APITOXINA & SISTEMA INMUNOLOGICO
| 1: Ann N Y Acad Sci. 2005 Nov;1056:279-92. |
Novel Drugs
and Vaccines Based on the Structure and Function of HIV Pathogenic Proteins
Including Nef.
Azad
AA.
Faculty of Health Sciences, Medical School, University of Cape Town, Anzio
Road, Observatory, 7925, Cape Town, South Africa. a_azad05@yahoo.com.au.
Evidence is presented to suggest that HIV-1 accessory protein Nef could be
involved in AIDS pathogenesis. When present in extracellular medium, Nef causes
the death of a wide variety of cells in vitro and may therefore be responsible
for the depletion of bystander cells in lymphoid tissues during HIV infection.
When present inside the cell, Nef could prevent the death of infected cells
and thereby contribute to increased viral load. Intracellular Nef does this
by preventing apoptosis of infected cells by either inhibiting proteins involved
in apoptosis or preventing the infected cells from being recognized by CTLs.
Neutralization of extracellular Nef could prevent the death of uninfected
immune cells and thereby the destruction of the immune system. Neutralization
of intracellular Nef could hasten the death of infected cells and help reduce
the viral load. Nef is therefore a very important molecular target for developing
therapeutics that slow progression to AIDS. The N-terminal region of Nef and
the naturally occurring bee venom mellitin have very similar primary and tertiary
structures, and they both act by destroying membranes. Chemical analogs of
a mellitin inhibitor prevent Nef-mediated cell death and inhibit the interaction
of Nef with cellular proteins involved in apoptosis. Naturally occurring bee
propolis also contains substances that prevent Nef-mediated cell lysis and
increases proliferation of CD4 cells in HIV-infected cultures. These chemical
compounds and natural products are water soluble and nontoxic and are therefore
potentially very useful candidate drugs.
PMID: 16387695 [PubMed - in process]
| 2: Eur J Immunol. 2005 Nov;35(11):3268-76. |
Prevention
of allergy by a recombinant multi-allergen vaccine with reduced IgE binding
and preserved T cell epitopes.
Karamloo F, Schmid-Grendelmeier P,
Kussebi F, Akdis M, Salagianni M,
von Beust BR,
Reimers A, Zumkehr J, Soldatova L,
Housley-Markovic Z,
Muller U, Kundig T, Kemeny DM, Spangfort MD,
Blaser K, Akdis CA.
Swiss
Novel approaches for the prevention of allergy are required, because of the
inevitably increasing prevalence of allergic diseases during the last 30 years.
Here, a recombinant chimeric protein, which comprises the whole amino acid
sequences of three bee venom major allergens has been engineered and used
in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m
1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping
amino acids were assembled in a different order in the Api m (1/2/3) chimeric
protein, which preserved entire T cell epitopes, whereas B cell epitopes of
all three allergens were abrogated. Accordingly, IgE cross-linking leading
to mast cell and basophil mediator release was profoundly reduced in humans.
Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less
type-1 skin test reactivity in allergic patients. Treatment of mice with Api
m (1/2/3) led to a significant reduction of specific IgE development towards
native allergen, representing a protective vaccine effect in vivo. These results
demonstrate a novel prototype of a preventive allergy vaccine, which preserves
the entire T cell epitope repertoire, but bypasses induction of IgE against
native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI
cross-linking in sensitized individuals.
| 3: In Vivo. 2005 Jul-Aug;19(4):801-5. |
Inhibitory effect
of whole bee venom in adjuvant-induced arthritis.
Lee
JY, Kang
SS, Kim
JH, Bae
CS, Choi
SH.
College of Veterinary Medicine and Research Institute of Veterinary Medicine,
Chungbuk National University, Republic of Korea.
The aim of this study was to assess the inhibitory effect of whole bee venom
(BV) on adjuvant-induced arthritis in the rat. Rats were divided into pre-apitherapy,
post-apitherapy and control experimental groups. The pre-apitherapy group
was subcutaneously stung with a honeybee (Apis mellifera L.) and the control
group was subcutaneously injected with 0.1 ml of physiological saline solution
one day prior to complete Freund's adjuvant (CFA) injection. The post-apitherapy
group was subcutaneously stung with a honeybee on day 14 after CFA injection.
When arthritis had developed in the rat, the post-apitherapy group was subcutaneously
administered whole BV every other day for a further 14 days. Clinical signs,
hematological values and radioglogical features were observed during the entire
experimental period. In the pre-apitherapy group, the development of inflammatory
edema and polyarthritis was inhibited. Significant differences in lameness
score, hind paw edema volume and radiological features were observed between
control and pre-apitherapy rats. White blood cell counts indicated that the
degree of leucocytosis was significantly different between the pre-apitherapy
and control groups (p < 0.01). Inflammatory edema, polyarthritis and bone
change into the right hind paw were effectively inhibited in pre-apitherapy
rats during the two-week period post-CFA injection. In conclusion, whole BV
was found to inhibit arthritic inflammation and bone changes in the rat. This
may be an alternative treatment for arthritis in humans.
PMID: 15999553 [PubMed - indexed for MEDLINE]
| 4: Brain Res. 2005 Jul 12;1049(2):210-6. |
The anti-inflammatory
effect of peripheral bee venom stimulation is mediated by central muscarinic
type 2 receptors and activation of sympathetic preganglionic neurons.
Yoon SY, Kim HW, Roh DH, Kwon YB, Jeong TO, Han HJ, Lee HJ, Choi SM, Ryu YH, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Seoul 151-742, South Korea.
The anti-inflammatory effect (AI) induced by peripheral injection of diluted
bee venom (dBV) involves activation of spinal cord circuits and is mediated
by catecholamine release from adrenal medulla, but the precise neuronal mechanisms
involved are not fully understood. In a recent study, we demonstrated that
an increase in spinal acetylcholine is involved in mediating the anti-inflammatory
effect of dBV and that this mediation also involves adrenomedullary activation.
The present study utilized the mouse air pouch inflammation model to evaluate
the involvement of spinal acetylcholine receptors and sympathetic preganglionic
neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT)
pretreatment with atropine (muscarinic cholinergic antagonist) but not hexamethonium
(nicotinic cholinergic antagonist) significantly suppressed dBVAI on zymosan-evoked
leukocyte migration. Subsequent experiments showed that IT pretreatment with
methoctramine (a muscarinic receptor type 2; M(2) antagonist), but not pirenzepine
(an M(1) antagonist) or 4-DAMP (an M(3) antagonist), suppressed the dBVAI.
In addition, dBV stimulation specifically increased Fos expression in SPNs
of the T7-T11, but not the T1-T6 or T12-L2 spinal cord segments, in animals
with zymosan-induced inflammation. Moreover, IT methoctramine pretreatment
suppressed this dBV-induced Fos expression specifically in SPNs of T7-T11
level. Peripheral sympathetic denervation using 6-hydroxydopamine (6-OHDA)
treatment (which spares sympathetic adrenal medullary innervation) did not
alter dBVAI. Collectively these results indicate that dBV stimulation leads
to spinal cord acetylcholine release that in turn acts on spinal M(2) receptors,
which via a hypothesized disinhibition mechanism activates SPNs that project
to the adrenal medulla. This activation ultimately leads to the release of
adrenal catecholamines that contribute to dBVAI.
PMID: 15953592 [PubMed - indexed for MEDLINE]
| 5: Int Immunopharmacol. 2005 Aug;5(9):1406-14. Epub 2005 Apr 20. |
Bee venom
modulates murine Th1/Th2 lineage development.
Nam
S, Ko E, Park
SK, Ko S, Jun
CY, Shin
MK, Hong
MC, Bae
H.
College of Oriental Medicine, Kyung Hee University, #1 Hoeki-dong Dongdaemoon-gu,
Seoul, 130-701, Korea.
Administration of bee venom (BV) elicits anti-inflammatory, anti-nociceptive
and anti-allergic effects in various animal models. This study was designed
to evaluate the direct effects of BV on helper T cell activities and on Th1/Th2
lineage development using both in vitro and in vivo conditions. In the Th1
skewed condition, BV increased the expression of IFN-gamma mRNA and enhanced
the expression of T-bet on purified CD4(+) T cells from splenocytes of BALB/c
mice. On the other hand, BV treatment did not alter the expression of IL-4
or GATA-
| 6: J Allergy Clin Immunol. 2005 May;115(5):1063-7. |
Increased
expression of osteopontin is associated with long-term bee venom immunotherapy.
Konno
S, Golden
DB, Schroeder
J, Hamilton
RG, Lichtenstein
LM, Huang
SK.
Johns
BACKGROUND: Venom allergen immunotherapy (VIT) is proven to be highly effective
for insect allergy, but the mechanisms and the biomarkers associated with
clinical efficacy remain elusive. OBJECTIVE: The aim of this study was to
identify candidate biomarkers associated with successful VIT. METHODS: Gene
chip array and clustering analyses of PBMCs from subjects with or without
VIT were performed. RESULTS: From gene chip array and clustering analyses,
an increased expression of osteopontin was found in patients who completed
5 to 6 years of VIT and discontinued therapy for 3 to 6 years (completed treatment
group) compared with the untreated group. A significantly higher level of
serum osteopontin was found in the completed treatment group compared with
the untreated group (n =
| 7: J Ethnopharmacol. 2005 May 13;99(1):157-60. |
Effects of
bee venom on the pro-inflammatory responses in RAW264.7 macrophage cell line.
Jang
HS, Kim
SK, Han
JB, Ahn
HJ, Bae
H, Min
BI.
Department of East-West Medicine, Graduate School, Kyung-Hee University, Seoul
130-701, South Korea.
The purpose of this study is to elucidate the molecular mechanism of anti-inflammatory
effect of bee venom (BV), which has been used for the treatment of various
inflammatory diseases in oriental medicine. With this aim, we examined the
effects of BV on the nitric oxide (NO) production by lipopolysaccharide (LPS)
or sodium nitroprusside in RAW264.7 macrophages. We further investigated the
effects of BV on the expression of inducible nitric oxide synthase (iNOS),
cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated
protein kinase (MAPK) with RT-PCR in LPS-stimulated RAW264.7 cells. BV suppressed
the NO production and decreased the levels of iNOS, COX-2, NF-kappaB and MAPK
mRNA in a dose-dependent manner. These results suggest that BV has an anti-inflammatory
effect by inhibiting iNOS and COX-2 expression, possibly through suppression
of NF-kappaB and MAPK expression.
PMID: 15848037 [PubMed - indexed for MEDLINE]
| 8: Clin Exp Allergy. 2005 Mar;35(3):367-73. |
Characterization
of the human T cell response to antigen 5 from Vespula vulgaris (Ves v 5).
Bohle B, Zwolfer B, Fischer GF, Seppala U, Kinaciyan T,
Bolwig C, Spangfort MD,
Ebner C.
Department of Pathophysiology,
Medical University of Vienna, VA-1090 Vienna, Austria. barbara.bohle@meduniwien.ac.at
BACKGROUND: The T cell reactivity to the major allergen of bee venom, phospholipase
A2, has been thoroughly characterized. In contrast, only little is known about
the human cellular response to major allergens from wasp venom. OBJECTIVE:
To characterize the human T cell response to antigen 5 from Vespula vulgaris,
Ves v 5. METHODS: Recombinant Ves v 5 was used to establish allergen-specific
T cell lines (TCL) and T cell clones (TCC) from the peripheral blood of vespid-allergic
and non-allergic individuals. Ves v 5-specific TCL were mapped for T cell
epitopes using overlapping synthetic peptides representing the complete amino
acid sequence of Ves v 5. Ves v 5-specific TCC were analysed for antigen-induced
secretion of IL-4, IFN-gamma and IL-10. RESULTS: Seventeen distinct T cell
epitopes were recognized by allergic individuals among which Ves v 5(181-192)
was identified as a dominant T cell epitope. Partially different epitopes
were observed in TCL from non-allergic subjects and the dominant epitope Ves
v 5(181-192) was not prevalent in these cultures. Ves v 5-specific TCC isolated
from allergic individuals did not show the typical T helper type 2 (Th2)-like
cytokine profile in response to specific stimulation, i.e. high amounts of
IL-4 and low IFN-gamma. TCC from non-allergic individuals showed a Th1-like
cytokine pattern. CONCLUSIONS: Our findings provide evidence that the allergic
T cell response to Ves v 5 is not Th2-dominated and that different immunogenic
sites on this major wasp venom allergen are recognized by allergic and non-allergic
individuals.
PMID: 15784117 [PubMed - indexed for MEDLINE]
| 9: FEBS Lett. 2005 Mar 14;579(7):1658-64. |
Cross-presentation
of a CMV pp65 epitope by human dendritic cells using bee venom PLA2 as a membrane-binding
vector.
Babon A, Almunia C, Boccaccio C,
Beaumelle B,
Gelb MH, Menez A, Maillere B, Abastado JP,
Salcedo M, Gillet D.
Protein Engineering and Research
Department (DIEP), bat 152, CEA-Saclay, 91191 Gif sur Yvette cedex, France.
We have used bee venom phospholipase A2 as a vector to load human dendritic
cells ex vivo with a major histocompatibility complex (MHC) class I-restricted
epitope fused to its C-terminus. The fusion protein bound to human monocyte-derived
dendritic cells and was internalized into early endosomes. In vitro immunization
experiments showed that these dendritic cells were able to generate specific
CD8 T cell lines against the epitope carried by the fusion protein. Cross-presentation
did not require proteasome, transporter associated with antigen processing,
or endosome proteases, but required newly synthesized MHC molecules. Comparison
of the antigen presentation pathway observed in this study to that followed
by other toxins used as vectors is discussed.
PMID: 15757657 [PubMed - indexed for MEDLINE]
| 10: J Allergy Clin Immunol. 2005 Feb;115(2):323-9. |
A major allergen
gene-fusion protein for potential usage in allergen-specific immunotherapy.
Kussebi F, Karamloo F, Rhyner C, Schmid-Grendelmeier P,
Salagianni M,
Mannhart C, Akdis M, Soldatova L,
Markovic-Housley Z,
Von Beust BR,
Kundig T, Kemeny DM, Blaser K, Crameri R, Akdis CA.
Swiss Institute of Allergy and
Asthma Research, Davos, Switzerland. fatimah.kussebi@charite.de
BACKGROUND: Specific immunotherapy is a common treatment of allergic diseases
and could potentially be applied to other immunologic disorders. Despite its
use in clinical practice, more defined and safer allergy vaccine preparations
are required. Differences between epitopes of IgE that recognize the 3-dimensional
structure of allergens and T cells that recognize linear amino acid sequences
provide a suitable tool for novel vaccine development for specific immunotherapy.
OBJECTIVE: The aim of the study was to delete B-cell epitopes and prevent
IgE crosslinking, but to preserve T-cell epitopes by fusion of 2 major allergens
of bee venom because of a change in the conformation. METHODS: By genetic
engineering, we produced a fusion protein composed of the 2 major bee venom
allergens: phospholipase A 2 (Api m 1) and hyaluronidase (Api m 2). RESULTS:
The Api m [1/2] fusion protein induced T-cell proliferation and both T H 1-type
and T H 2-type cytokine responses. In contrast, IgE reactivity was abolished,
and profoundly reduced basophil degranulation and type 1 skin test reactivity
was observed. Pretreatment of mice with Api m [1/2] fusion protein significantly
suppressed the development of specific IgE as well as other antibody isotypes
after immunization with the native allergen. CONCLUSION: The novel fusion
protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE
FcepsilonRI crosslinking and protects from IgE development.
PMID: 15696088 [PubMed - indexed for MEDLINE]
| 11: Arthritis Rheum. 2004 Nov;50(11):3504-15. |
Antiarthritic
effect of bee venom: inhibition of inflammation mediator generation by suppression
of NF-kappaB through interaction with the p50 subunit.
Park
HJ, Lee
SH, Son
DJ, Oh KW, Kim
KH, Song
HS, Kim
GJ, Oh GT, Yoon
do Y, Hong
JT.
College of Pharmacy, Chungbuk National University, 48 Gaesin-dong, Heungduk-gu,
Cheongju, Chungbuk 361-763, South Korea.
OBJECTIVE: To investigate the molecular mechanisms of the antiarthritic effects
of bee venom (BV) and melittin (a major component of BV) in a murine macrophage
cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid
arthritis. METHODS: We evaluated the antiarthritic effects of BV in a rat
model of carrageenan-induced acute edema in the paw and in a rat model of
chronic adjuvant-induced arthritis. The inhibitory effects of BV and melittin
on inflammatory gene expression were measured by Western blotting, and the
generation of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) and the intracellular
calcium level were assayed. NF-kappaB DNA binding and transcriptional activity
were determined by gel mobility shift assay or by luciferase assay. Direct
binding of BV and melittin to the p50 subunit of NF-kappaB was determined
with a surface plasmon resonance analyzer. RESULTS: BV (0.8 and 1.6 mug/kg)
reduced the effects of carrageenan- and adjuvant-induced arthritis. This reducing
effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 mug/ml)
and melittin (5 and 10 mug/ml) on lipopolysaccharide (LPS; 1 mug/ml)-induced
expression of cyclooxygenase 2, cytosolic phospholipase A(2), inducible NO
synthase, generation of PGE(2) and NO, and the intracellular calcium level.
BV and melittin prevented LPS-induced transcriptional and DNA binding activity
of NF-kappaB via the inhibition of IkappaB release and p50 translocation.
BV (affinity [K(d)] = 4.6 x 10(-6)M) and melittin (K(d) = 1.2 x 10(-8)M) bound
directly to p50. CONCLUSION: Target inactivation of NF-kappaB by directly
binding to the p50 subunit is an important mechanism of the antiarthritic
effects of BV.
PMID: 15529353 [PubMed - indexed for MEDLINE]
| 12: J Allergy Clin Immunol. 2004 Oct;114(4):943-50. |
Modulation
of allergic responses in mice by using biodegradable poly(lactide-co-glycolide)
microspheres.
Jilek
S, Walter
E, Merkle
HP, Corthesy
B.
Department of Chemistry and Applied BioSciences, Swiss Federal Institute of
Technology Zurich, Zurich, Switzerland.
BACKGROUND: Biodegradable poly(lactide- co -glycolide) (PLGA) microspheres
are a promising carrier for vaccine delivery capable of maturing antigen-presenting
cells to stimulate T-cell-mediated immune responses. However, the potential
of microspheres to downregulate an allergic response in vivo is unknown. OBJECTIVE:
The aim of this study was to determine whether microspheres could potentiate
DNA vaccination against allergy and to evaluate the immunomodulatory properties
of microspheres alone. METHODS: Mice were treated prophylactically with DNA-loaded
plain PLGA microspheres before sensitization with phospholipase A2 (PLA2),
the major allergen of bee venom. PLA2-specific IgG1, IgG2a, IgE in serum were
measured for 8.5 months, and splenocyte proliferative responses and cytokine
profiles were determined. Protection against anaphylaxis was evaluated after
injection of an otherwise lethal dose of PLA2. RESULTS: Phospholipase A2-specific
IgG1 and IgG2a production turned out to be 2 times higher using cationic microspheres
compared with anionic microspheres, but was not influenced by the presence
of DNA. In contrast, reduction in IgE production and T-cell hyporesponsiveness
were observed with all microsphere formulations. Recall challenge with PLA2
triggered combined expression of both IL-4 and IFN-gamma, together with sustained
expression of IL-10 that can explain the protective effect against anaphylaxis.
CONCLUSION: Our data suggest a dual mechanism that does initially rely on
a TH2 to TH1 immune deviation and then on IL-10-mediated suppression. This
is the first physiological demonstration that plain PLGA microspheres can
induce tolerance in mice for as long as 6 months postsensitization.
PMID: 15480340 [PubMed - indexed for MEDLINE]
| 13: Protein Sci. 2004 Nov;13(11):2970-8. Epub 2004 Sep 30. |
Alteration
of the tertiary structure of the major bee venom allergen Api m 1 by multiple
mutations is concomitant with low IgE reactivity.
Buhot
C, Chenal
A, Sanson
A, Pouvelle-Moratille
S, Gelb
MH, Menez
A, Gillet
D, Maillere
B.
Protein Engineering and Research Department, batiment 152, CEA-Saclay, 91191
Gif sur Yvette, France.
We have engineered a recombinant form of the major bee venom allergen (Api
m 1) with the final goal of reducing its IgE reactivity. This molecule (Api
mut) contains 24 mutations and one deletion of 10 amino acids. The successive
introduction of these sequence modifications led to a progressive loss of
specific IgE and IgG reactivity and did not reveal any immunodominant epitopes.
However, Api mut exhibited a clear loss of reactivity for Api m 1-specific
IgE and IgG. Injection of Api mut into mice induced specific antibody production.
This humoral response was as high as that induced by the Api m 1 but the cross-reactivity
of the antibodies was weak. As inferred by far UV circular dichroism, this
mutant was correctly folded. However, near UV circular dichroism and denaturation
curves of Api mut showed that it exhibits a dynamic tertiary structure and
that it is a highly flexible molecule. Finally, as all the sequence modifications
have been introduced outside the human and murine T cell epitope regions,
we investigated its T cell properties in mice. We showed that Api mut-specific
T lymphocytes induced in vivo were stimulated in vitro by both proteins. These
data provide new insights in the design of hypoallergenic molecules.
PMID: 15459335 [PubMed - indexed for MEDLINE]
| 14: Allergy. 2004 Oct;59(10):1110-7. |
The CD63
basophil activation test in Hymenoptera venom allergy: a prospective study.
Sturm
GJ, Bohm
E, Trummer
M, Weiglhofer
I, Heinemann
A, Aberer
W.
Department of Experimental and Clinical Pharmacology, University of Graz,
Graz, Austria.
BACKGROUND: The basophil activation test (BAT), which relies on flow cytometric
quantitation of the allergen-induced up-regulation of the granule-associated
marker CD63 in peripheral blood basophils, has been suggested to be a useful
approach in detecting responsiveness to allergens. The purpose of this study
was to establish the usefulness of the BAT with regard to the clinical history
and current diagnostic tools in Hymenoptera venom allergy using a prospective
study design. METHODS: Fifty-seven consecutive patients allergic to Hymenoptera
venom as defined by a systemic reaction after an insect sting, and 30 age-
and sex-matched control subjects with a negative history were included. The
degree and nature of sensitization was confirmed by skin testing, specific
immunoglobulin E (IgE), serum tryptase levels and BAT. In the nonallergic
control group only analysis of specific IgE and BAT were performed. Correlation
of BAT, skin test and specific IgE, respectively, with the clinical history
in the allergic group was termed as sensitivity and in the control group as
specificity. RESULTS: Twenty one of 23 (91.3%) bee venom allergic patients
and 29 of 34 (85.3%) patients allergic to wasp and hornet venom tested positive
in BAT. The overall sensitivity of BAT, specific IgE and skin tests were 87.7,
91.2 and 93.0%, respectively. The overall specificities were 86.7% for BAT
and 66.7% for specific IgE. No correlation between the severity of clinical
symptoms and the magnitude of basophil activation was observed. CONCLUSION:
The BAT seems to be an appropriate method to identify patients allergic to
bee or wasp venom with a comparable sensitivity to standard diagnostic regimens.
The higher specificity of BAT as compared with specific IgE makes this test
a useful tool in the diagnosis of Hymenoptera venom allergy.
Publication Types:
PMID: 15355471 [PubMed - indexed for MEDLINE]
| 15: Allergy. 2004 Oct;59(10):1102-9. |
The basophil
activation test in wasp venom allergy: sensitivity, specificity and monitoring
specific immunotherapy.
Erdmann
SM, Sachs
B, Kwiecien
R, Moll-Slodowy
S, Sauer
I, Merk
HF.
Department of Dermatology and Allergology, University Hospital of Aachen,
Aachen, Germany.
BACKGROUND: As in vitro diagnosis of wasp venom sensitization by specific
serum IgE has a sensitivity of only 60-80%, additional in vitro tests are
desirable. Basophil activation is associated with the expression of CD63 and
its measurement has been proposed as a novel in vitro test for immediate-type
allergy. Furthermore, to date, no in vitro test exists to monitor successful
specific immunotherapy (SIT) with wasp venom. Therefore, the potentially harmful
sting challenge is still recommended. OBJECTIVE: We compared the CD63-based
basophil activation test (BAT) in the diagnosis of wasp venom allergy with
skin tests and measurement of specific IgE. Furthermore, we investigated whether
BAT can predict the outcome of the sting challenge in patients on SIT. METHODS:
Fifty patients with a systemic reaction caused by a wasp sting and 20 controls
were studied. Intracutaneous tests were performed with wasp and bee venom
in the suspected allergics. Specific IgE was determined by the CAP-FEIA method
and basophil activation by flow cytometry upon double staining with anti-IgE/anti-CD63
mAb. Twenty-five patients were sting challenged 6 months after starting SIT
and the BAT was repeated before challenge. RESULTS: Sensitivity of the intracutaneous
tests, specific IgE and BAT was 100, 76, and 92%, respectively. Specificity
of specific IgE and the BAT was 85 and 80%, respectively. The cut-off for
a positive BAT was 15% CD63+ basophils. There was a positive correlation between
IgE reactivity to wasp venom and the number of CD63+ basophils (r = 0.65).
Although no patient had a systemic reaction upon sting challenge, in most
subjects basophil activation did not decrease when compared with the BAT before
SIT. CONCLUSIONS: Quantitation of basophil activation by CD63 expression is
a valuable new in vitro method for diagnosis of allergy to hymenopteran venoms.
The CD63-based BAT is a helpful tool for the complementation of routine diagnostic
tests such as specific IgE as it increases sensitivity of in vitro detection
of sensitization. However, this in vitro method does not offer an alternative
to the sting challenge in monitoring successful SIT.
PMID: 15355470 [PubMed - indexed for MEDLINE]
| 16: Am J Chin Med. 2004;32(3):361-7. |
Anti-inflammatory
effect of bee venom on type II collagen-induced arthritis.
Lee JD, Kim SY, Kim TW, Lee SH, Yang HI, Lee DI, Lee YH.
Research Group of Pain and Neuroscience
in Vision 2000 Project East-West Medical Research Institute, Kyung Hee University,
Seoul, Korea. ljdacu@khmc.or.kr
Bee venom (BV) has been used to relieve pain and reduce inflammation in traditional
Oriental medicine, especially in chronic inflammatory diseases such as rheumatoid
arthritis (RA). We previously reported that the BV injection into a traditional
acupuncture point (Zusanli) reduced arthritis-associated edema and nociceptive
responses in Freund's adjuvant-induced arthritis in rats (Kwon et al., 2001).
This study was designed to evaluate the anti-inflammatory and anti-cytokine
effect of BV on a murine type-II collagen-induced arthritis (CIA) model. Male
mice were immunized by spontaneous injection of 100 microg of an emulsion
of bovine type-II collagen and complete Freund's adjuvant (CFA), with a booster
injection after 2 weeks. In the experimental group, 0.1 ml BV was injected
at acupuncture point (Zusanli) near both knees twice a week for a total of
5 times. In the control group, normal saline was injected at the same frequencies.
These injections began 5 weeks after the first collagen injection. Starting
the 3rd week after the first collagen injection, we examined limb swelling
and severity of arthritis twice a week. At 8 weeks, mice were sacrificed and
synovial tissue was examined with the light microscope and serum cytokines
(IL-1beta and TNF-alpha) were measured by ELISA. The incidence of arthritis,
the mean arthritis index and the number of arthritic limbs were significantly
lower in the treatment compared to the control group (63% versus 75%, 3.4%
versus 8.5%, 23% versus 75%, respectively). Among the serum proinflammatory
cytokines, the production of TNF-alpha in the BV group was suppressed compared
to the control group (59 +/- 4.5 versus 99.5 +/- 6.5, p < 0.05), but IL-1beta
was not suppressed. The examination of the histopathology of the joints of
murine CIA showed decreased inflammation signs and less lymphocyte infiltration
after BV acupuncture therapy. Acupuncture therapy with BV suppressed the development
of arthritis and caused inhibition of the immune responses in type-II collagen-induced
arthritis.
PMID: 15344419 [PubMed - indexed for MEDLINE]
| 17: Clin Exp Allergy. 2003 Sep;33(9):1209-15. |
Impaired
secretion of interleukin-4 and interleukin-13 by allergen-specific T cells
correlates with defective nuclear expression of NF-AT2 and jun B: relevance
to immunotherapy.
Faith
A, Richards
DF, Verhoef
A, Lamb
JR, Lee
TH, Hawrylowicz
CM.
Department of Respiratory Medicine and Allergy, The Guy's, King's College
and St Thomas' Hospitals School of Medicine, London, UK. alex.faith@kcl.ac.uk
BACKGROUND: Allergen immunotherapy (IT) is a successful treatment associated
with decreased Th2 cytokine production by allergen-specific T cells. We have
previously demonstrated (Faith et al., J Immunol 1997; 159:53-57) that inhibition
of Th2 cytokine production in vitro correlates with impaired tyrosine kinase
activity through the TCR. The transcription factor complex, nuclear factor
of activated T cells (NF-AT), which regulates Th2 cytokine production is controlled
by the activity of tyrosine kinases. OBJECTIVE: To address whether decreased
Th2 cytokine production by allergen-specific CD4+ T cells following IT is
correlated with altered translocation and nuclear expression of the NF-AT
family member, NF-AT2, and the activator protein 1 (AP1) component of NF-AT,
jun B. METHODS: T cell lines specific for insect venom phospholipase A2 (PLA)
were derived from patients prior to and during conventional venom IT. Nuclear
expressions of NF-AT and jun B were assessed following stimulation through
the TCR. Th1 and Th2 cytokine and IL-10 production by insect venom-specific
T cells were also determined. Results were compared with a well-established
model system in which anergy was induced in cloned, allergen-specific Th2
cells. RESULTS: Impaired translocation and decreased expression of NF-AT2
and jun B were detected in PLA-specific T cell lines derived from bee venom-allergic
individuals following 16 weeks treatment compared to pre-treatment. These
results correlated with significantly reduced production of IL-4 and IL-13
and significantly increased production of IFN-gamma and IL-10 by PLA-specific
T cells. Impaired IL-4 and IL-13 production also correlated with defective
nuclear expression of NF-AT2/jun B in cloned, anergic allergen-specific Th2
cells. CONCLUSION: These results suggested that optimal production of IL-4
and IL-13 by allergen-specific T cells is dependent on the nuclear expression
of NF-AT2 and jun B. Thus, specific inhibition of NF-AT2/jun B might be an
option in novel and improved forms of allergen IT.
PMID: 12956740 [PubMed - indexed for MEDLINE]
| 18: J Allergy Clin Immunol. 2003 Jun;111(6):1255-61. |
Induction
of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.
Francis
JN, Till
SJ, Durham
SR.
Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College,
Dovehouse Street, London SW3 6LY, UK.
BACKGROUND: Immunotherapy involves the modulation of allergen-specific T-cell
responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated
patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing
CD4+CD25+ regulatory T cells have emerged as potential mediators of immune
tolerance in numerous murine models of immunopathology. OBJECTIVE: The aim
of this study was to evaluate the role of IL-10 production and CD4+CD25+ T
cells in the response to grass pollen immunotherapy. METHODS: PBMCs were isolated
from patients after 1 year of grass pollen immunotherapy and from matched
untreated atopic and healthy control subjects. After 6 days of in vitro stimulation
with Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation
and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated
for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and
assessed for intracellular IL-10 by means of flow cytometry. RESULTS: Patients
undergoing immunotherapy produced significantly more IL-10 than atopic control
subjects (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic
patients, 30 +/- 5 pg/mL [n = 11]; P <.001), and the number of CD4+CD25+
cells identified after allergen stimulation was also greater in the immunotherapy
group. The numbers of CD4+CD25+ T cells correlated positively with activation
as measured by proliferation in both of the control groups but not in the
immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy
were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+
cells. CONCLUSION: Grass pollen immunotherapy results in a population of circulating
T cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen
restimulation.
Publication Types:
PMID: 12789226 [PubMed - indexed for MEDLINE]
| 19: Toxicon. 2003 Jun;41(7):861-70. |
Inhibition
of mammary carcinoma cell proliferation in vitro and tumor growth in vivo
by bee venom.
Orsolic
N, Sver
L, Verstovsek
S, Terzic
S, Basic
I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, 10 000 Zagreb, Croatia. norsolic@yahoo.com
The possible tumor growth- and metastasis-inhibiting effects of bee venom
in mice and in tumor cell cultures were studied. The tumor was a transplantable
mammary carcinoma (MCa) of CBA mouse. Intravenous administration of bee venom
to mice significantly reduced the number of metastases in the lung. However,
subcutaneous administration of bee venom did not reduce the number of lung
metastases, indicating that the antitumor effect of the venom could be highly
dependent on the route of injection as well as close contact between the components
of the venom and the tumor cells, as was shown by in vitro studies on MCa
cells. We also observed variations in immunological parameter induced by bee
venom. We proposed that bee venom has an indirect mechanism of tumor growth
inhibition and promotion of tumor rejection that is based on stimulation of
the local cellular immune responses in lymph nodes. Apoptosis, necrosis, and
lysis of tumor cells are other possible mechanisms by which bee venom inhibits
tumor growth.
PMID: 12782086 [PubMed - indexed for MEDLINE]
| 20: FASEB J. 2003 Jun;17(9):1026-35. |
T helper
(Th) 2 predominance in atopic diseases is due to preferential apoptosis of
circulating memory/effector Th1 cells.
Akdis
M, Trautmann
A, Klunker
S, Daigle
I, Kucuksezer
UC, Deglmann
W, Disch
R, B