Exogenous type-1 cytokines modulate mercury-induced hyper-IgE in the rat

Suppression of IgE responses is a major goal for immunotherapy, especially in the field of allergy. The Th2 subset of helper T cells plays a vital rol e in class switching of B cells to IgE production by releasing IL-4. In sus ceptible rat strains, mercuric chloride (HgCl2) induces activation of Th2 c ells, with enhanced expression of IL-4, polyclonal B cell activation and ve ry high levels of circulating IgE. We have previously shown that spontaneou s regulation of this response coincides with enhanced expression of Th1/typ e-1 cytokines, including interferon-gamma (IFN-gamma) and IL-12. We now rep ort the effects of administration of exogenous type-1 cytokines on HgCl2-in duced Th2 responses. At high doses, recombinant rat IFN-gamma markedly redu ced serum IgE levels. Recombinant mouse IL-12 was less effective at suppres sing the IgE response following HgCl2, although it caused marked up-regulat ion of IFN-gamma gene expression in the spleen. In Lewis rats, which are re sistant to HgCl2-induced autoimmunity, a rise in serum IFN-gamma was observ ed after HgCl2, but administration of polyclonal anti-IFN-gamma antibodies did not render them susceptible to induction of a Th2 response by HgCl2. Ou r data show that individual type-1 cytokines are capable of suppressing the dramatic Th2 response induced by HgCl2 in the rat, even when they are not given until after starting HgCl2 administration. IFN-gamma is a pivotal cyt okine in ameliorating the Th2 response and measures aimed at selective up-r egulation of this cytokine may be of therapeutic value in suppression of un wanted IgE responses.