title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Immunopathology Unit, Medical Research Centre, Cambridge, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: McHugh
authors.forename: J
authors.initials: J
authors.lastname: Deighton
authors.forename: A G
authors.initials: AG
authors.lastname: Stewart
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: P W
authors.initials: PW
authors.lastname: Ewan
mesh_terms: D001514:Bee Venoms / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D015203:Reproducibility of Results; D013268:Stimulation, Chemical; D013299:Streptodornase and Streptokinase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D001514:Bee Venoms; D010835:Phytohemagglutinins; D015847:Interleukin-4; D007371:Interferon-gamma; D013299:Streptodornase and Streptokinase