Document 0236
 DOCN  M9650236
 TI    Bee venom immunotherapy induces a shift in cytokine responses from a
       TH-2 to a TH-1 dominant pattern: comparison of rush and conventional
       immunotherapy.
 DT    9605
 AU    McHugh SM; Deighton J; Stewart AG; Lachmann PJ; Ewan PW; Molecular
       Immunopathology Unit, Medical Research Centre,; Cambridge, UK.
 SO    Clin Exp Allergy. 1995 Sep;25(9):828-38. Unique Identifier : AIDSLINE
       MED/96105566
 AB    BACKGROUND: The mechanism of immunotherapy is unclear. Allergic disease
       is known to involve enhanced TH-2 cytokine responses to allergen.
       OBJECTIVE: In order to investigate the mechanisms of immunotherapy, we
       have examined changes in cytokine secretion before (13 patients) and
       during (nine patients) both rush and conventional venom immunotherapy
       (VIT) in bee venom allergic patients. METHODS: Peripheral blood
       mononuclear cells were stimulated in vitro with bee venom, non-specific
       antigen or mitogen and secretion of IL-4 (TH-2) and IFN gamma (TH-1)
       over the culture period measured. RESULTS: Untreated patients had TH-2
       responses to venom and TH-1 responses to antigen and strong
       proliferative responses to venom. Controls showed no response
       (proliferation or cytokines) to venom and the normal TH-1 response to
       antigen. VIT resulted in marked changes in cytokine secretion to venom,
       with reduction of the abnormal TH-2 response and induction of a TH-1
       response. The pattern differed in rush and conventional VIT. One day
       after rush VIT there was a significant fall in IL-4 secretion (P <
       0.01), which rose by 3 weeks then declined. In conventional VIT there
       was a gradual reduction of IL-4 production significant after 2 months
       and undetectable by 6 months. IFN gamma secretion was induced by VIT.
       Proliferative responses mirrored the IL-4 changes. One day after rush
       VIT there was a loss of T cells, monocytes and NK cells from peripheral
       blood. CONCLUSION: This study shows that immunotherapy shifted cytokine
       responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting
       direct effects on T cells. How these cytokine changes relate to clinical
       desensitization is not clear. In the longer term they would result in an
       isotype switch from IgE to IgG. Early changes in cytokine or chemokine
       production might downregulate mast cell or basophil reactivity and
       explain the rapid desensitization in rush VIT.
 DE    Bee Venoms/*THERAPEUTIC USE  Cells, Cultured  Comparative Study  Female
       Human  Immunotherapy/*METHODS  Interferon Type
       II/BIOSYNTHESIS/*SECRETION  Interleukin-4/BIOSYNTHESIS/*SECRETION
       Lymphocyte Transformation/DRUG EFFECTS  Male
       Phytohemagglutinins/PHARMACOLOGY  Reproducibility of Results
       Stimulation, Chemical  Streptodornase and Streptokinase/PHARMACOLOGY
       Support, Non-U.S. Gov't  T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY  Th1
       Cells/DRUG EFFECTS/IMMUNOLOGY/*SECRETION  Th2 Cells/DRUG
       EFFECTS/IMMUNOLOGY/*SECRETION  CLINICAL TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).