LEAD DIFFERENTIALLY MODIFIES CYTOKINE PRODUCTION IN-VITRO AND IN-VIVO

An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impa ired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 respon se. Lead, another metal toxicant, causes enhanced B cell activities an d impairs host resistance to several bacterial and viral infections. I n addition, Pb was reported to enhance Th2 proliferation and inhibit T h1 proliferation. The differential effects of Pb on Th subset activati on have been further investigated. In vitro IL-4 production by a Th2 c lone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl 2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo IL-4 production by anti-CD3-stimulated splenic T cells was enhanced, but I FN gamma production was inhibited. Additionally, the plasma IL-4 and I gE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exo genous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 pr oduced similar findings. This study is the first report of the prefere ntial activation of a Th2 response by Pb in vivo and suggests that Pb, like Hg, may induce autoimmune responses by upsetting the balance bet ween Th1- and Th2-like cells, which could enhance production of antibo dies to Self antigens. (C) 1996 Academic Press, Inc.