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IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC).
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 1997 May; Vol. 108 (2), pp. 375-80. - Publication Year :
- 1997
-
Abstract
- 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.
- Subjects :
- Adult
Antibodies, Antinuclear biosynthesis
Cells, Cultured
DNA immunology
Female
Humans
Immunoglobulin G drug effects
Immunoglobulin M drug effects
Interferon-gamma pharmacology
Interleukin-10 pharmacology
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Middle Aged
Immunoglobulin G biosynthesis
Immunoglobulin M biosynthesis
Interleukin-12 pharmacology
Leukocytes, Mononuclear immunology
Lupus Erythematosus, Systemic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9104
- Volume :
- 108
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 9158113
- Full Text :
- https://doi.org/10.1046/j.1365-2249.1997.d01-1009.x