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
Sm. Mchugh et al., 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, Clinical and experimental allergy, 25(9), 1995, pp. 828-838
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.