Effect of flurbiprofen on cytokine production by human monocytes and U-937 and THP-1 cell lines.
Possible effects of nonsteroidal antiinflammatory drugs (NSAID) on inflammatory mediators other than arachidonic acid metabolites which might contribute to the antiinflammatory effects of these drugs have not been fully explored. We investigated the effects of an NSAID, flurbiprofen, on production of the cytokines tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by human peripheral blood monocytes and by the human cell lines U-937 and THP-1. Cytokine production was induced by 1 microgram/ml bacterial lipopolysaccharide (LPS) in both monocytes and cell lines, and cytokine levels in supernatants were measured by enzyme immunoassay. In monocytes, IL-6 was the major product while in both cell lines, TNF alpha was the major product. Flurbiprofen caused moderate inhibition of IL-1 beta and TNF alpha production by stimulated monocytes, but did not affect IL-6 production. In contrast, flurbiprofen completely abolished IL-6 production by both cell lines and substantially inhibited IL-1 beta and TNF alpha production. These observations raise the possibility that inhibition of cytokine production by flurbiprofen may contribute to the antiinflammatory properties of this drug.
Lozanski
G
G
Department of Medicine, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109.
Ballou
S P
SP
Kushner
I
I
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005480:Flurbiprofen / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology*; D009000:Monocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005480:Flurbiprofen