Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes.
We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.
Berger
S
S
Senckenberg Center of Pathology, University of Frankfurt am Main, Germany. S.Berger@em.uni-frankfurt.de
Chandra
R
R
Balló
H
H
Hildenbrand
R
R
Stutte
H J
HJ
D000936:Antigen-Antibody Complex / Q000502:physiology*; D000941:Antigens / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology; D013743:Tetanus Antitoxin / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D000941:Antigens; D016207:Cytokines; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D011453:Prostaglandins; D013743:Tetanus Antitoxin; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12