Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats.

Abstract

Cells producing a T(H2)-cytokine profile play an important role in the onset and maintenance of atopic diseases, and therefore specific immunotherapy is aimed to induce a switch to cells producing a T(H1)- or T(H0)-cytokine profile. Recently, a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed, but its mechanisms of action are unknown. We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests (PD20FEV1) with a standardized Fel d 1 cat extract on Fel d 1-specific serum IgE and IgG levels and in vitro IL-4 and IFN-gamma production. Patients allergic to cats received 6 weekly injections of 7.5 micro(g) (low dose), 75 micro(g) (medium dose), or 750 micro(g) (high dose) of Fel d 1 peptides (25 patients) or a placebo (6 patients). Six weeks after ending immunotherapy, posttreatment PD20FEV1 was not significantly different between the treated and placebo groups. However, in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days. IL-4 release was significantly reduced in the high dose-treated group (P <.005, Wilcoxon W test), whereas it was unchanged in the low or medium dose- and in the placebo-treated groups. In all groups, IFN-gamma, IgE, and IgG levels remained unchanged. There was no correlation between the improvement of PD20FEV1 and the decrease in IL-4 production. These data suggest that peptide immunotherapy may act by shifting the Fel d 1-induced response of PBMCs in vitro from the T(H2)-like to the T(H0)-like phenotype.