Selective effects of some 5-lipoxygenase inhibitors on synovial interleukin-1 (IL-1) production compared with IL-1 synthesis inhibitors (original) (raw)

Abstract

To determine the role of 5-LO regulation of IL-1 in synovial tissues, we examined the effects of 5-LO inhibitors compared with standard IL-1 synthesis inhibitors on IL-1 production by human synovial tissue explants from patients with inflammatory arthropathies. MK886, L-656,224, PF-5901, and tepoxalin all inhibited IL-1 production in concentrations up to 10 μ_M_, whereas other 5-LO inhibitors (ICI-211,965, zileuton), as well as IL-1 synthesis inhibitors (IX-207,887, tenidap), were inactive. LT products, thus regulate IL-1 production and inhibition thereof is one strategy for inhibiting this cytokine.

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References

  1. S. R. Brandwein,Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J. Biol. Chem.261, 8624–8623 (1986).
    PubMed Google Scholar
  2. B. McDonald, L. Loose and L.J. Rosenwasser,The influence of a novel arachidonate inhibitor, CP66,248, on the production and activity of human monocyte IL-1. Arth. Rheum.31 (Suppl. 4), 517 (1988).
    Google Scholar
  3. I. G. Otterness, T. J. Garty and L. D. Loose,Tenidap: A new drug for arthritis. In_Therapeutic Approaches to Inflammatory Diseases_. (Eds. A. J. Lewis, N. S. Doherty and N. R. Ackerman) pp. 229–241. Elsevier, Amsterdam (1989).
    Google Scholar
  4. T. Hoffman, Y. L. Lee, E. F. Lizzio, A. K. Tripathi, J. J. Jessop, M. Taplits, T. G. Abrahamsen, C. S. Carter and J. Puri,Absence of modulation of monokine production via exogenous cyclooxygenase or 5-lipoxygenase metabolites—MK-886 (3-[1-(4-chlorobenzyl)-3-tert-butyl-thio-5-isopro-pylindol-2-yl]-2,2-dimethylpropanoic acid), indomethacin, or arachidonate fail to alter immunoreactive interleukin-1 beta, or TNF-alpha production by human monocytes in vitro. Clin. Immunol. Immunopathol.58, 399–408 (1991).
    Article PubMed Google Scholar
  5. J. Schnyder, P. Bollinger and T. G. Payne,Inhibition of monokine release by IX 207-887. Agents and Actions_29_, 108–110 (1990).
    Article PubMed Google Scholar
  6. S. J. Hopkins and M. Humphreys,Simple, sensitive and specific bioassay of interleukin-1. J. Immunol. Meth.120, 271–276 (1989).
    Article Google Scholar
  7. S. J. Hopkins, I. Holt and M. Humphreys,Removal of inhibitory activity and determination of biologically active interleukin-1 in biological fluids. In_The Physiological and Pathological Effects of Cytokines_. (Eds. C. A. Dinarello, M. J. Kluger, M. C. Powander and J. J. Oppenheim) pp. 7–12. Wiley-Liss, New York 1990.
    Google Scholar

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Authors and Affiliations

  1. Department of Biomedical Sciences, McMaster University Health Sciences Centre and Osler Institute, L8N 3Z5, Hamilton, Ontario, Canada
    K. D. Rainsford & C. Ying
  2. Department of Pathology, McMaster University Health Sciences Centre and Osler Institute, L8N 3Z5, Hamilton, Ontario, Canada
    K. D. Rainsford
  3. Department of Surgery, McMaster University Health Sciences Centre and Osler Institute, L8N 3Z5, Hamilton, Ontario, Canada
    F. Smith

Authors

  1. K. D. Rainsford
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  2. C. Ying
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  3. F. Smith
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Rainsford, K.D., Ying, C. & Smith, F. Selective effects of some 5-lipoxygenase inhibitors on synovial interleukin-1 (IL-1) production compared with IL-1 synthesis inhibitors.Agents and Actions 39 (Suppl 1), C186–C188 (1993). https://doi.org/10.1007/BF01972761

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