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

Abstract

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.

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

“…PGE 2 synthesis is relied on intracellular COX including COX1 and COX2, which possess both fatty acid COX activity and PG hydroperoxidase activity. Although, IC/Ig-mediated the production of PGE 2 has been reported by several times (30,31), we were still amazed by the amount of PGE 2 by IC/Ig. Next, we demonstrated that IC/Ig induced the rapid and durative expression of COX1 and COX2 in macrophages, which may account for the reason why so large amounts of PGE 2 was induced.…”

Activation of Natural Interferon-α Producing Cells by Apoptotic U937 Cells Combined with Lupus IgG and its Regulation by Cytokines

“…An induction of IL-10 might be anticipated in active SLE because immune complexes [31,43] as well as apoptotic cells [32,33] can cause IL-10 production in human PBMC in vitro. However, in the present study we failed to detect as determined by immunoassay, significant levels of IL-10 produced by PBMC stimulated by the combination of apoptotic U937 cells and SLE-Igb.…”

“…It has been shown that immune complexes can induce IL-10 production [31]. Furthermore apoptotic cells can produce IL-10 [32,33] as well as promote production of IL-10 in PBMC [34].…”

Both Th1 and Th2 Cytokines Affect the Ability of Monoclonal Antibodies To Protect Mice againstCryptococcus neoformans

“…Given the potent anti-inflammatory role of IL-10, it is possible that the decreased survival we observed in the antibody-treated IL-10 Ϫ/Ϫ mice resulted from increased inflammation induced by immune complexes formed when the exogenous antibody to GXM was administered. Immune complexes induce the release of many proinflammatory cytokines such as IL-1␤, IL-6, and TNF-␣, as well as IL-10 and vasoactive substances such as platelet-activating factor (3,4,74). In the absence of the inhibition of inflammation that is usually caused by IL-10, these mediators may act unopposed, thereby causing intense inflammatory damage to the host.…”