Human alveolar macrophage and blood monocyte inhibition of fibroblast proliferation. Evidence for synergy between interleukin-1 and tumor necrosis factor.
Stimulated human blood monocytes and alveolar macrophages are known to elaborate a soluble factor(s) that inhibits fibroblast proliferation by stimulating fibroblast prostaglandin (PG) production. However, the factor(s) mediating these effects has never been completely characterized and its relationship to known cytokines has never been fully defined. In this study, we demonstrate that this factor(s) is partially trypsin-sensitive, is between 16 and 24 kilodaltons molecular weight, and elutes between 0.13 and 0.25 M NaCl and 24 and 38% 1-propanol from anion exchange and reverse phase columns, respectively. In addition, we demonstrate that interleukin-1 (IL-1) and tumor necrosis factor (TNF) have similar patterns of elution and that the fibroblast growth-inhibiting and PGE-stimulating activities in monocyte and alveolar macrophage supernatants are partially reversed with neutralizing antibodies against IL-1-beta or TNF. However, this inhibition is not due to IL-1-beta or TNF, alone, because each has a mild stimulatory effect on fibroblast proliferation. In contrast, a dose-dependent inhibition of fibroblast proliferation is noted when fibroblasts are simultaneously exposed to recombinant IL-1 and TNF. This inhibition is reversed when fibroblast PG production is blocked and appears to result from IL-1 and TNF synergistically stimulating fibroblast PGE production. Thus, the PG-mediated inhibition of fibroblast proliferation caused by stimulated human mononuclear phagocytes is not the result of a single cytokine but is instead at least partly mediated by an interaction of IL-1 and TNF.
Elias
J A
JA
Cardiovascular-Pulmonary Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283.
Gustilo
K
K
Freundlich
B
B
D000941:Antigens / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*
D000941:Antigens; D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha