Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells.
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-alpha. Freshly isolated rat peritoneal mast cells will produce IL-6 in response to anti-IgE, LPS, PGE1, or PGE2; 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-alpha 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-alpha 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 PGE1- and PGE2-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 IC50 for LPS- or anti-IgE-activated cells (0.21 ng/ml) and cells activated with a combination of LPS and PGE2 (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.
Marshall
J S
JS
Intestinal Disease Research Programme, McMaster University, Health Science Centre, Hamilton, Ontario, Canada.
Leal-Berumen
I
I
Nielsen
L
L
Glibetic
M
M
Jordana
M
M
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D006636:Histamine Release; D007073:Immunoglobulin E / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007073:Immunoglobulin E; D000527:Alprostadil