MERCURY-INDUCED AUTOIMMUNITY IN THE ABSENCE OF IL-4

In susceptible H-2(s) mice, mercuric chloride (HgCl2) induces an autoi mmune syndrome characterized by production of anti-nucleolar antibodie s (ANoA) and increased serum levels of IgG1 and IEE antibodies. The in crease in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in the induction of this syndrome. We have pr eviously shown that administration of IL-12, a potent Th1-promoting cy tokine, resulted in a dramatic reduction of the HgCl2-induced anti-nuc leolar antibody titres and inhibited serum IgG1 increase. These result s suggest that Tn1 T cells can down-regulate ANoA, and support a role for the Th2 subset in ANoA production, possibly via IL-4. To examine t he role of IL-4 in this syndrome, C57B1/6 mice (H-2(b)) with a targete d deletion of the IL-4 gene were mated with A.SW mice (H-2(s)) to yiel d H-2(s) mice lacking IL-4. We then analysed ANoA and serum immunoglob ulin levels in these mice after HgCl2 treatment. While mercury-treated IL-4(-/-) H-2(s) mice had virtually no detectable serum IgG1 or IgE, and very low levels of IgG1 ANoA, these mice had levels of IgG2a and I gG2b class ANoA comparable to mercury-treated IL-4(+) H-2(s) mice, ind icating that IL-4 is not required for the ANoA response in mercury-ind uced autoimmunity.