Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: a network of pro- and anti-inflammatory cytokines dependent on the antigen:antibody ratio.
We have used two experimental models of immune complexes to study the secretion of interleukin (IL)-10, IL-6 and their connection with the immune complex-induced synthesis of prostaglandin (PG) E2 by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. PGE2 could augment the immune complex-induced IL-6 and IL-10 secretion, but alone, did not induce cytokine secretion. IL-10 was capable of down-regulating the release of IL-6 and PGE2. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. All three regulatory factors examined here share anti-inflammatory properties and are closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well-known ability no cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/Th2 responses.
Berger
S
S
Senckenberg Center of Pathology, University of Frankfurt am Main, Frankfurt, Germany.
Balló
H
H
Stutte
H J
HJ
D000936:Antigen-Antibody Complex / Q000276:immunology*; D001782:Blood Donors; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology*; D011458:Prostaglandins E / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D015850:Interleukin-6; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10