Interleukin-1 and tumor necrosis factor synergistically stimulate lung fibroblast interleukin-1 alpha production.
We determined whether normal human lung fibroblasts expressed cell-associated thymocyte-stimulating activity in response to recombinant interleukin-1 (rIL-1) (alpha and beta) and recombinant tumor necrosis factor (rTNF). Individually, rIL-1 and rTNF induced fibroblast expression of thymocyte-stimulating activity, with rIL-1 being significantly more potent. Importantly, combining rIL-1 and rTNF resulted in a synergistic increase in fibroblast thymocyte-stimulating activity. This synergistic interaction was dose dependent for both cytokines and was not noted when gamma-interferon was combined with rIL-1 or rTNF. In all cases, the thymocyte-stimulating activity was the result of an IL-1 alpha-like moiety whose maximal production required protein synthesis. IL-1 alpha activity could be detected after as little as 4 h, peaked after 24 h, and returned toward normal with longer periods of cytokine-fibroblast incubation. However, cytokine-stimulated fibroblasts that no longer expressed IL-1 alpha activity could be induced to re-express this activity with repeat cytokine challenge. Induction of fibroblast IL-1 alpha by IL-1 and/or TNF may be an important mechanism amplifying IL-1-mediated biologic events at sites of local inflammation.
Elias
J A
JA
Department of Internal Medicine, Hospital of the University of Pennsylvania, Philadelphia.
Reynolds
M M
MM
D002448:Cell Adhesion; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000502:physiology*; D011994:Recombinant Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide