Synergistic stimulation of fibroblast prostaglandin production by recombinant interleukin 1 and tumor necrosis factor.
Mononuclear cell production of cytokines that stimulate fibroblast prostaglandin (PG) elaboration is an important mechanism by which mononuclear cells regulate fibroblast function. However, the soluble factors mediating these PG-stimulatory effects are incompletely understood. We characterized the effects on PG production by confluent normal lung fibroblasts of recombinant interleukin 1 alpha (IL 1 alpha), interleukin 1 beta (IL 1 beta) and tumor necrosis factor (TNF), alone and in combination. All three cytokines stimulated fibroblast PG production with both IL 1 peptides being significantly more potent than TNF. In addition, TNF interacted in a synergistic fashion with both IL 1 peptides to augment fibroblast PGE elaboration further. The stimulatory effects of the cytokines were almost entirely caused by an increase in PGE2 production and were reversed when the cytokine(s) were removed. These changes in PG production could not be explained by alterations in cell number and were completely negated by specific anticytokine antibodies. Recombinant gamma interferon, although synergizing with TNF in regulating other cellular functions, did not interact with TNF to augment fibroblast PGE elaboration. In addition, the synergistic interaction of IL 1 and TNF did not extend to all biologic effects of IL 1 since TNF did not augment the ability of IL 1 to stimulate thymocyte proliferation.
D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000502:physiology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011994:Recombinant Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D007375:Interleukin-1; D011453:Prostaglandins; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha