TH1 TH2 CYTOKINE GENE-EXPRESSION AFTER MERCURIC-CHLORIDE IN SUSCEPTIBLE AND RESISTANT RAT STRAINS/

Mercuric chloride (HgCl2) has contrasting effects on different rat str ains: susceptible strains, e.g. Brown Norway (BN) develop polyclonal B cell activation, multiple autoantibodies and widespread tissue injury . Lewis (LEW) rats are resistant: no autoimmune response occurs after HgCl2; instead, there is immunosuppression. We have previously shown, by fully quantitative polymerase chain reaction (PCR), up-regulation o f interleukin-4 (IL-4) gene expression in HgCl2-treated BN rats, impli cating Th2 cells in the autoimmune syndrome. Involvement of the recipr ocal Th1 subset, producing interferon-gamma (IFN-gamma). in resistance of LEW rats to HgCl2 has been suggested. We now report extensive anal ysis of Th1 and Th2 cytokine gene expression in spleen and lymph nodes of susceptible (BN) and resistant (LEW) rats after HgCl2. IL-4 and IF N-gamma were analyzed by quantitative PCR, other cytokines were assess ed using semiquantitative PCR: the relative merits of these two techni ques are discussed. We show pronounced up-regulation of IL-4 and more modest up-regulation of IFN-gamma In BN rats, but no up-regulation of either in LEW rats. Baseline levels of IFN-gamma were higher in LEW ra ts. Semi-quantitative PCR showed increased expression of IL-2, IL-G an d IL-10 in BN; in LEW rats only ILIO was increased. There was no marke d change in IL-5, IL-13 or transforming growth factor-beta (TGF-beta) in either strain, These data further support the key role of IL-4 in H gCl2-induced autoimmunity, and suggest that failure of up-regulation o f IL-4, together with higher baseline IFN-gamma expression, accounts f ur resistance of LEW rats to HgCl2. However; neither IFN-gamma nor TGF -beta can be implicated in HgCl2-induced immunosuppression in the LEW rat in vivo: our data suggest a role for IL-10 in this phenomenon.