21st European Workshop for Rheumatology Research
- Meeting abstract
Immune complex stimulation of peripheral blood mononuclear cells result in enhancement of suppression of IL-12 production dependent on soluble serum factors
Arthritis Research & Therapy volume 3, Article number: P027 (2001)
Immune complexes can induce the production of various cytokines in vitro. Both IL-10 and IL-12 could be induced by addition of heat-aggregated immunoglobulins to mononuclear cells in serum-free cell culture systems. Addition of native serum to the cell cultures influenced the effects on IL-10 and IL-12 in opposite ways. While IL-10 levels were increased in cell cultures with native human serum, IL-12 production was inhibited as compared to cultures with monomeric IgG. Two series of experiments suggested that the effects of immune complexes on IL-12 production depended on the activity of the classical complement pathway in the serum: 1.) Heat-inactivation of serum reverted the inhibitory effect of immune complexes on IL-12 production. 2.) C4 deficient serum behaved as a heat-inactivated normal serum concerning the effects on IL-12 production, and this effect could be reversed by addition of C4. The effects of neutralizing IL-12 had modest effect on immune complex-induced IL-10 production, and the effects of neutralizing IL-10 had no effect on IL-12 production. IL-10 production in the presence of immune complexes could be partially blocked by anti-FcgammaRII antibodies, while the immune complex-mediated effects on IL-12 not changed by blocking FcgammaRII or FcgammaRIII.
Opposite and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in cytokine-dependent autoimmune diseases like rheumatoid arthritis or systemic lupus erythematosus, where local or systemic activation of the classical complement pathway participate in the disease processes. Blocking of complement activation or receptors for activated complement components might gain increased attention as potential targets for immune therapies in the light of such cytokine-deviating effects.
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Tejde, A., Nilsson Ekdahl, K., Nilsson, B. et al. Immune complex stimulation of peripheral blood mononuclear cells result in enhancement of suppression of IL-12 production dependent on soluble serum factors. Arthritis Res Ther 3 (Suppl 2), P027 (2001). https://doi.org/10.1186/ar196