Regulation of in vitro anti-DNA antibody production by a novel disease modifying anti-rheumatic drug, Lobenzarit.
Lobenzarit (CCA) is a novel disease modifying anti-rheumatic drug. Although CCA has been shown to prevent the development of the autoimmune disorders in NZB/W F1 mice and in MRL/l mice, the precise mechanism of its action has not yet been clarified. The current study examined the effect of CCA on the in vitro production of anti-DNA antibody, a hallmark of the autoimmune disorders. In vitro anti-DNA antibody production was induced from highly purified B cells of normal human individuals by stimulation with Staphylococcus aureus and CD4+ T cells or with immobilized anti-CD3 activated CD4+ T cells. CCA suppressed the production of anti-DNA antibody as well as IgM at pharmacologically obtainable concentrations (10-50 micrograms/ml). CCA did not inhibit the initial stages of B cell activation in either culture system, but rather suppressed the maturation of previously activated B cells. Although CCA suppressed IL2 production by immobilized anti-CD3 activated CD4+ T cells, its suppressive effects on B cells were not overcome by the addition of IL2 or factors generated from mitogen activated T cells (TF). CCA did not suppress IL6 production by immobilized anti-CD3 activated CD4+ T cells nor that by B cells activated with SA+ IL2. These results indicate that CCA suppresses the production of anti-DNA antibody by directly inhibiting activated B cells. The data therefore suggest the possible efficacy of CCA in suppressing the function of activated B cells in human SLE patients.
Hirohata
S
S
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism; D013211:Staphylococcus aureus / Q000502:physiology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000974:Antibodies, Antinuclear; D007075:Immunoglobulin M; D007376:Interleukin-2; D015850:Interleukin-6; D062367:ortho-Aminobenzoates; D012217:Rheumatoid Factor; C015735:lobenzarit