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.

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

NICOLETTI, FERDINANDO;
2000

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/12876
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