Interleukin-1 (IL-1) receptor blockade reduces endotoxin and Borrelia burgdorferi-stimulated IL-8 synthesis in human mononuclear cells.
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 beta, 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 beta-, 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 beta-induced IL-8 synthesis was observed when IRAP was added 60 or 90 min after IL-1 beta; 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
R
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Poutsiaka
D D
DD
Miller
L C
LC
Granowitz
E V
EV
Dinarello
C A
CA
D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002478:Cells, Cultured; D004731:Endotoxins; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D011863:Radioimmunoassay; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins
D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C044101:endotoxin, Escherichia coli