Effect of a Novel Non-steroidal Anti-inflammatory Drug (M-5011) on Cytokine Levels in Rats With Monosodium Urate Crystal-Induced Pleurisy

Access this Article

Author(s)

Abstract

We evaluated the effects of a new non-steroidal anti-inflammatory drug (NSAID), <I>d</I>-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), and indomethacin on the production of arachidonate metabolites and pro-inflammatory cytokines in male Sprague-Dawly rats with monosodium urate crystal (MSU)-induced pleurisy. Levels of tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 in the pleural exudate were determined by biological assays, while prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), leukotriene B<SUB>4</SUB> (LTB<SUB>4</SUB>) and cytokine-induced chemoattractant-1 (CINC-1) levels were quantified by enzyme immunoassays. Orally administered M-5011 (5 mg/kg) decreased the pleural exudate volume at 3 and 4 hr after MSU injection. Indomethacin (10 mg/kg) decreased the volume at 3 - 5 hr. These drugs reduced the number of leukocytes in the pleural cavity at 6 hr. Both NSAIDs also reduced the content of PGE<SUB>2</SUB> in the exudate without affecting LTB<SUB>4</SUB> levels. Increased productions of both IL-6 and CINC-1 in the exudate were reduced by pretreatment with M-5011 or indomethacin, and TNF levels in the exudate were increased by pretreatment of these drugs. Thus, M-5011 inhibits the production of both IL-6 and CINC-1 at lower doses than those of indomethacin, and the inhibitory effect of M-5011 on CINC-1, but not IL-6, may partly contribute to the inhibition of leukocyte infiltration in rats with MSU-induced pleurisy.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(4), 439-446, 1999-04-01

    The Japanese Pharmacological Society

References:  32

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008683438
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4706041
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top