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

Background The mechanism of immunotherapy is unclear. Allergic disease is known to involve enhanced TH-2 cytokine responses to allergen. Obj ective In order to investigate the mechanisms of immunotherapy, we hav e examined changes in cytokine secretion before (13 patients) and duri ng (nine patients) both rush and conventional venom immunotherapy (VIT ) in bee venom allergic patients. Methods peripheral blood mononuclear cells were stimulated ipl 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 respo nses to venom. Controls showed no response (proliferation or cytokines ) to venom and the normal TH-I response to antigen. VIT resulted in ma rked changes in cytokine secretion to venom, with reduction of the abn ormal TH-2 response and induction of a TH-I response. The pattern diff ered 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 t hen 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 mirror ed the IL-4 changes. One day after rush VIT there was a loss of T cell s, 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-I dominant pattern, suggesting direct effects on T cell s. How these cytokine changes relate to clinical desensitization is no t clear. In the longer term they would result in an isotype switch fro m IgE to IgG. Early changes in cytokine or chemokine production might downregulate mast cell or basophil reactivity and explain the rapid de sensitization in rush VIT.