Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells.

Abstract

Mast cells have been implicated in a number of diseases involving chronic inflammation including asthma, rheumatoid arthritis, and inflammatory bowel diseases. They are a potent source of several cytokines, including IL-6 and TNF-␣ . Freshly isolated rat peritoneal mast cells will produce IL-6 in response to anti-IgE, LPS, PGE 1 , or PGE 2 ; however, the mechanisms by which such cytokine production is regulated are poorly understood. IL-10 is recognized as an important immunoregulatory cytokine with effects on T cell development and the production of inflammatory cytokines. IL-10 has previously been described to enhance mast cell development in the context of IL-3 and IL-4. In the current study, we have examined the ability of IL-10 to modulate rat peritoneal mast cell IL-6 and TNF-␣ production in response to a variety of stimuli. We have observed that recombinant murine IL-10 can inhibit the production of both IL-6 and TNF-␣ by mast cells without altering the degree of histamine release in response to anti-IgE. Concentrations of IL-10 as low as 0.2 ng/ml were sufficient to inhibit IL-6 production by LPS-or anti-IgE-activated cells significantly. IL-10 also inhibited PGE 1 -and PGE 2 -induced IL-6 production. The relative potency of IL-10 as an inhibitor of mast cell IL-6 production was highly dependent upon the stimulus used, with a 10-fold difference in the IC 50 for LPS-or anti-IgEactivated cells (0.21 ng/ml) and cells activated with a combination of LPS and PGE 2 (2.29 ng/ml). This suggests that prostanoids may limit the ability of IL-10 to modulate mast cell IL-6 production in the context of inflammation. These data have important implications for the regulation of mast cell IL-6 in inflammatory diseases involving prostanoid production and the effects of treatment with cyclooxygenase inhibitors. Our results also demonstrate a dual role for IL-10 on mast cells as a growth factor and inhibitor of cytokine production. ( J. Clin. Invest. 1996. 97:1122-1128.)

IL-10 plays an important role as an immune-modulator in the pathogenesis of atopic diseases

“…A role for IL-10 in the regulation of immune responses to allergens was first suggested by studies revealing that IL-10 inhibited cytokine production by eosinophils stimulated with LPS (19). Later, it was demonstrated that IL-10 might also inhibit the production of cytokines, such as TNF and IL-6, by stimulated mast cells (20,21). IL-10 inhibits monocyte major histocompatibility complex-class (MHCclass II), B7.1 (CD80), B7.2 (CD88), intercellular adhesion molecule-1, and CD23 expression and accessory cell function (22).…”

Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A2 and Cyclooxygenase

“…Macrophage viability was determined by trypan blue exclusion as described elsewhere (Korzeniewsky & Callewaert 1983;Marshall et al 1996). Macrophage viability ranged from 89 to 97% in the different various experiments.…”

Neuroprotective effects of phosphatidylcholine and L-alpha-glycerylphosphorylcholine in experimental inflammation

“…Th e pro-infl ammatory mediator release may be counteracted by increased IL-10 production, which downregulates TNF-α activity, inhibits long-term IL-6 production (Marshall et al 1996, Huaux et al 1999, blocks NF-κ B activity, and is involved in the regulation of the Janus kinase/signal…”

“…Th e spread of pro-infl ammatory events is balanced by the release of anti-infl ammatory cytokines such as interleukin-10 (IL-10), which downregulates TNF-α activity and inhibits long-term interleukin-6 (IL-6) production (Marshall et al 1996, Huaux et al 1999. Indeed, it has been demonstrated that the TNF-α output peaks after 2 -8 h and has usually returned to the baseline by 24 h after radiation (Daigle et al 2001).…”