Inhibition of monocyte IL-1 production by the anti-inflammatory compound, SK&F 86002

doi:10.1016/0192-0561(88)90007-0

International Journal of Immunopharmacology

Volume 10, Issue 7, 1988, Pages 835-843

International Journa...

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Abstract

The effects of several anti-inflammatory/anti-arthritic drugs on the in vitro production of interleukin-1 (IL-1) by human monocytes were examined. SK&F 86002, a novel dihydroimidazo thiazoline which inhibits both 5-lipoxygenase- and cyclooxygenase-mediated arachidonate metabolism was shown to be a potent inhibitor of IL-1 production by LPS-stimulated human monocytes. The inhibition was dose-dependent $(ic_{50} = 1.30 ± 1 μ M)$ , reversible and was independent of the concentration or type of stimulus used. The compound also inhibited cell-associated IL-1 activity. The compound did not exert general inhibitory effects on such parameters as adherence, cytotoxic function and protein synthesis of the monocytes. Other cyclooxygenase and/or 5-lipoxygenase inhibitors of arachidonic acid metabolism tested, with the exception of nordihydroguaiaretic acid, were inactive in inhibiting monocyte IL-1 production suggesting that the inhibition of IL-1 production by 86002 may be dissociated from its inhibition of the fatty acid oxygenases. The inhibition of IL-1 production by SK&F 86002 adds another facet of drug action contributing to its spectrum of anti-inflammatory activities.

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International Journal of Immunopharmacology

Abstract

References (20)

The influence of lipoxygenase inhibitors on the in vitro production of human leukocyte pyrogen and lymphocyte activating factor (IL-1)

Int. J. Immunopharmac.

SK&F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid

Biochem. Pharmac.

Agents that increase cellular cAMP inhibit production of IL-2, but not its activity

Biochem. biophys. Res. Commun.

A modified assay for Interleukin-1

J. Immun. Meth.

Nucleotide sequence of human monocyte interleukin 1 precursor cDNA

Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. I. Effectors belong to the monocyte/macrophage lineage

J. Immun.

Pharmacologic characterization of the anti-inflammatory profiles of a new dual inhibitor of lipoxygenase and cyclooxygenase

Agents Actions

Interleukin-1

Rev. infect. Dis.

Induction of acute phase reactants by interleukin-1

Adv. Inflamm. Res.

Arachidonic acid-induced inflammation: inhibition by dual inhibitor of arachidonic acid metabolism, SK&F 86002

Inflammation

Cited by (69)

Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells

Small-molecule therapeutics in rheumatoid arthritis: Scientific rationale, efficacy and safety

Targeting kinases: A new approach to treating inflammatory rheumatic diseases

Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease

Progress in achieving proof of concept for p38 kinase inhibitors

Progress in achieving proof of concept for p38 kinase inhibitors