IL-4 is required for the IgE and IgG1 increase and IgG1 autoantibody formation in mice treated with mercuric chloride.
Previous studies have established that in susceptible mouse strains, such as A.SW (H-2s), repeated injections of subtoxic doses of HgCl2 induce increased serum levels of total IgE and IgG1, high serum titers of antinuclear autoantibodies (ANo1A), and immune-complex glomerulonephritis. Moreover, it has been shown that susceptibility is determined by H-2As and that Th cells are required for the induction of these immunopathologic alterations by HgCl2. In the present study we showed that treatment in vivo with anti-IL-4 mAb completely abrogated the HgCl2-induced increase in total IgE and partially inhibited the increase in IgG1, but failed to suppress the increase in IgG2A. Furthermore, we showed that IL-4 influences the pattern of IgG subclass distribution among ANo1A of HgCl2-treated mice. Whereas treatment with anti-IL-4 mAb significantly reduced the titers of IgG1 ANolA, it increased those of IgG2A, IgG2B, and IgG3 ANolA. Thus, these results show that IL-4 contributes to the optimal formation in vivo of murine IgG1 and that it is involved in the autoantibody formation of a systemic autoimmune disease. The available evidence suggests that HgCl2 induces an increased production of IL-4 by Th2 cells. If this is correct, it implies that MHC class II alleles determine whether the preferential response to HgCl2 is made by Th1 or Th2 cells and, hence, the type of immunopathologic alterations ensuing.
Ochel
M
M
Division of Immunology, Heinrich Heine University of Düsseldorf, Federal Republic of Germany.
Vohr
H W
HW
Pfeiffer
C
C
Gleichmann
E
E
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000139:chemically induced*; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride