Effect of SK&F 86002 on cytokine production by human monocytes.
Human monocytes respond to a variety of stimuli in vitro by producing a number of physiologically important macromolecules including the cytokines. SK&F 86002, a dual inhibitor of the arachidonate metabolism, has been shown to inhibit LPS induced IL-1 production in human monocytes. We examined its effect on the production of other cytokines which are coordinately expressed as a result of LPS stimulation such as tumor necrosis factor alpha (TNF), alpha interferon (IFN-A), interferon beta-2 (IL-6) and granulocyte colony stimulating factor (g-CSF). The IC50 of SK&F 86002 for the TNF production was 5-8 microM, and greater than 20 microM for the other three cytokines. These IC50s were significantly higher than that previously reported for IL-1 production (1-2 microM). Taken together these data indicate that the inhibitory effect of SK&F 86002 on IL-1 production is selective and the production of cytokines in drug treated monocytes can be differentially affected.
Lee
J C
JC
Department of Immunology, Smith Kline & French Laboratories, Swedeland, PA 19479.
Rebar
L
L
Laydon
J T
JT
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001685:Biological Factors / Q000096:biosynthesis*; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D046508:Culture Techniques; D016207:Cytokines; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007370:Interferon Type I / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D007093:Imidazoles; D007370:Interferon Type I; D007376:Interleukin-2; D008070:Lipopolysaccharides; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole