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Interleukin‐1 (IL‐1) is a potent stimulator of IL‐8 production by fibroblasts and monocytes. In the present study, we asked how much of endotoxin (LPS)‐induced IL‐8 production by human peripheral blood mononuclear cells was due to IL‐1 induced by LPS. Cells were stimulated with either IL‐1 β , LPS, or Borrelia burgdorferi , and total IL‐8 was determined by a specific radioimmunoassay. The addition of saturating concentrations of IL‐1 receptor antagonist protein (IRAP) reduced the IL‐1 β ‐, LPS‐, and B. burgdorferi ‐induced IL‐8 synthesis by 85, 50, and 40%, respectively. Increasing the concentration of LPS did not affect the reduction in IL‐8 synthesis observed in the presence of IRAP. Significant inhibition of the IL‐1 β ‐induced IL‐8 synthesis was observed when IRAP was added 60 or 90 min after IL‐1 β ; similarly, IL‐8 synthesis after LPS was also reduced by delayed addition of IRAP. These data suggest that the ameliorative effects of IL‐1 receptor blockade in models of inflammation and infection may be due, in part, to suppression of IL‐1‐induced IL‐8.—Porat, R.; Poutsiaka, D. D.; Miller, L. C.; Granowitz, E. V.; Dinarello, C. A. Interleukin‐1 (IL‐1) receptor blockade reduces endotoxin and Borrelia burgdorferi ‐stimulated IL‐8 synthesis in human mononuclear cells. FASEB J. 6: 2482‐2486; 1992.
Porat et al. (1992) studied this question.