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 role in class switching of B cells to IgE production by releasing IL-4. In susceptible rat strains, mercuric chloride (HgCl 2) induces activation of Th2 cells, with enhanced expression of IL-4, polyclonal B cell activation and very high levels of circulating IgE. We have previously shown that spontaneous regulation of this response coincides with enhanced expression of Th1/type-1 cytokines, including interferon-gamma (IFN-γ) and IL-12. We now report the effects of administration of exogenous type-1 cytokines on HgCl 2- induced Th2 responses. At high doses, recombinant rat IFN-γ markedly reduced serum IgE levels. Recombinant mouse IL-12 was less effective at suppressing the IgE response following HgCl 2, although it caused marked up-regulation of IFN-γ gene expression in the spleen. In Lewis rats, which are resistant to HgCl 2-induced autoimmunity, a rise in serum IFN-γ was observed after HgCl 2, but administration of polyclonal anti-IFN-γ antibodies did not render them susceptible to induction of a Th2 response by HgCl 2. Our data show that individual type-1 cytokines are capable of suppressing the dramatic Th2 response induced by HgCl 2 in the rat, even when they are not given until after starting HgCl 2 administration. IFN-γ is a pivotal cytokine in ameliorating the Th2 response and measures aimed at selective up-regulation of this cytokine may be of therapeutic value in suppression of unwanted IgE responses.
|Titolo:||Exogenous type-1 cytokines modulate mercury-induced hyper-IgE in the rat|
|Data di pubblicazione:||2000|
|Citazione:||Exogenous type-1 cytokines modulate mercury-induced hyper-IgE in the rat / Gorrie M.J.; Qasim F.J.; Wiiittle C.J.; Gillespie K.M.; Szeto; C.-C.; Nicoletti F; Bolton E.M.; Bradley J.A.; Mathieson P.W. - In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. - ISSN 0009-9104. - 121:1(2000), pp. 17-22.|
|Appare nelle tipologie:||1.1 Articolo in rivista|