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Related Experiment Videos

Does rofecoxib increase TNF-alpha levels?

S Nalbant1, I Akmaz, M Kaplan

  • 1Gata Heh Iç Hastaliklari Servisi, Haydarpaşa, Istanbul, Turkey. nalbantselim@hotmail.com

Clinical and Experimental Rheumatology
|September 8, 2006
PubMed
Summary
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Rofecoxib (Vioxx) and other NSAIDs reduced inflammation in rats, but rofecoxib unexpectedly increased tumor necrosis factor alpha (TNF-alpha) levels. Further research is needed to determine if elevated TNF-alpha explains cardiovascular risks associated with COX-2 inhibitors.

Area of Science:

  • Pharmacology
  • Immunology
  • Inflammation Research

Background:

  • Rofecoxib (Vioxx), a COX-2 selective NSAID, was withdrawn due to increased myocardial infarction risk.
  • The mechanism behind this cardiovascular risk remains unclear.
  • Tumor necrosis factor alpha (TNF-alpha) is implicated in myocardial infarction mortality.

Purpose of the Study:

  • To investigate the effect of rofecoxib on TNF-alpha levels.
  • To utilize a rat subcutaneous air pouch model with MSU crystal-induced inflammation.

Main Methods:

  • Rats were induced with inflammation using MSU crystals in air pouches.
  • Groups received rofecoxib, indomethacin, or diclofenac.
  • Leukocyte counts, histology, IL-10, and TNF-alpha levels were measured.

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Main Results:

  • All NSAIDs reduced white blood cell counts and vascularity.
  • TNF-alpha levels significantly increased in all drug groups, with the highest in the rofecoxib group.
  • Interleukin-10 (IL-10) levels significantly decreased in all drug groups.

Conclusions:

  • NSAIDs demonstrated anti-inflammatory effects in the MSU crystal model.
  • Rofecoxib tended to elevate TNF-alpha levels.
  • The role of increased TNF-alpha in COX-2 inhibitor side effects requires further investigation.