IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC).
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by polyclonal B cell activation and by the production of anti-double-stranded (ds) DNA antibodies. Given the inhibitory effects of IL-12 on humoral immune responses, we investigated whether IL-12 displayed such an activity on in vitro immunoglobulin production by SLE PBMC. Spontaneous IgG, IgG1, IgG2, IgG3 and IgM antibody production was dramatically reduced by addition of IL-12. These results were confirmed by Elispot assays detecting IgG- and anti-dsDNA-secreting cells. While IL-6 and TNF titres measured in PBMC supernatants were not modified by addition of IL-12, interferon-gamma (IFN-gamma) titres were up-regulated and IL-10 production down-regulated. Since addition of IFN-gamma did not down-regulate immunoglobulin production and since the inhibitory activity of IL-12 on immunoglobulin synthesis was not suppressed by anti-IFN-gamma antibody, we concluded that the effect of IL-12 on immunoglobulin production was not mediated through IFN-gamma. Our data also argue against the possibility that down-regulation of endogenous IL-10 production was responsible for the effect of IL-12. Thus, inhibition of IL-10 production by IFN-gamma was not accompanied by inhibition of immunoglobulin production, and conversely, restoration of IL-10 production by anti-IFN-gamma antibody did not suppress the inhibitory activity exerted by IL-12 on immunoglobulin production. Taken together, our data indicate that reduction of excessive immunoglobulin and anti-dsDNA antibody production by lupus PBMC can be achieved in vitro by IL-12, independently of IFN-gamma and IL-10 modulation.
Houssiau
F A
FA
Rheumatology Unit, Louvain Medical School, Brussels, Belgium.
Mascart-Lemone
F
F
Stevens
M
M
Libin
M
M
Devogelaer
J P
JP
Goldman
M
M
Renauld
J C
JC
D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000187:drug effects; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008875:Middle Aged
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA