Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system.
Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcgamma RII antibodies, whereas Fcgamma R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.
Unit of Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
A
A
Tejde
L
L
Mathsson
K N
KN
Ekdahl
B
B
Nilsson
J
J
Rönnelid
D000936:Antigen-Antibody Complex / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002478:Cells, Cultured; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D005719:gamma-Globulins / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D015850:Interleukin-6; D017452:Receptors, IgG; D005719:gamma-Globulins; D016753:Interleukin-10; D018664:Interleukin-12