Open AccessIL‐12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC)
Author(s) -
HOUSSIAU F. A.,
MASCARTLEMONE F.,
STEVENS M.,
LIBIN M.,
DEVOGELAER J.P.,
GOLDMAN M.,
RENAULD J.C.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.d01-1009.x
Subject(s) - elispot , peripheral blood mononuclear cell , antibody , immunology , immune system , immunoglobulin g , polyclonal antibodies , biology , systemic lupus erythematosus , in vitro , t cell , medicine , biochemistry , disease
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‐γ) titres were up‐regulated and IL‐10 production down‐regulated. Since addition of IFN‐γ did not down‐regulate immunoglobulin production and since the inhibitory activity of IL‐12 on immunoglobulin synthesis was not suppressed by anti‐IFN‐γ antibody, we concluded that the effect of IL‐12 on immunoglobulin production was not mediated through IFN‐γ. 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‐γ was not accompanied by inhibition of immunoglobulin production, and conversely, restoration of IL‐10 production by anti‐IFN‐γ 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‐γ and IL‐10 modulation.