Mercury‐induced autoimmunity in the absence of IL‐4
In susceptible H‐2s mice, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by production of anti‐nucleolar antibodies (ANoA) and increased serum levels of IgG1 and IgE antibodies. The increase 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 previously shown that administration of IL‐12, a potent Th1‐promoting cytokine, resulted in a dramatic reduction of the HgCl2‐induced anti‐nucleolar antibody titres and inhibited serum IgG1 increase. These results suggest that Th1 T cells can down‐regulate ANoA, and support a role for the Th2 subset in ANoA production, possibly via IL‐4. To examine the role of IL‐4 in this syndrome, C57Bl/6 mice (H‐2b) with a targeted deletion of the IL‐4 gene were mated with A.SW mice (H‐2s) to yield H‐2s mice lacking IL‐4. We then analysed ANoA and serum immunoglobulin levels in these mice after HgCl2 treatment. While mercury‐treated IL‐4−/− H‐2s mice had virtually no detectable serum IgG1 or IgE, and very low levels of IgG1 ANoA, these mice had levels of IgG2a and IgG2b class ANoA comparable to mercury‐treated IL‐4+ H‐2s mice, indicating that IL‐4 is not required for the ANoA response in mercury‐induced autoimmunity.