Effects of an ophthalmic formulation of meloxicam on COX-2 expression, PGE2 release, and cytokine expression in a model of acute ocular inflammation

Br J Ophthalmol. 2008 Jan;92(1):120-5. doi: 10.1136/bjo.2007.125179. Epub 2007 Oct 25.

Abstract

Aim: To determine the efficacy of meloxicam ophthalmic formulation on COX-2 activity and expression, inflammation-related cytokines expression and inflammation in an ocular inflammation model.

Methods: Ocular inflammation was induced in New Zealand rabbits by topical application of croton oil (3%) for 3 h. An ophthalmic solution of 0.03% meloxicam, 0.1% sodium diclofenac or vehicle (Sophisen) was administered every 4 h. Conjunctiva, cornea, aqueous humour and vitreous humour were collected.

Results: In irritated eyes, 72 h of meloxicam treatment downregulated COX-2 expression and activity (mRNA by RT-PCR and PGE2 levels by ELISA, respectively) in a time-dependent manner and reduced inflammation. Meanwhile, diclofenac failed to reduce COX-2 mRNA or PGE2 to basal levels after 7 days of treatment. Meloxicam treatment downregulated IL-6 and IFN-gamma expression in the conjunctiva and IL-1beta and TNF-alpha expression in the cornea. Diclofenac failed to modify these cytokines in both tissues. Meloxicam treatment increased the expression of IL-6 in conjunctiva, and IL-10 in cornea, while diclofenac had no effect on these cytokines.

Conclusion: Meloxicam treatment was more efficient than diclofenac in downregulating the expression and activity of COX-2, reducing inflammation, and modifying the inflammatory-related cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aqueous Humor / metabolism
  • Cornea / drug effects
  • Cornea / metabolism
  • Cornea / pathology
  • Croton Oil
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dinoprostone / metabolism*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Endophthalmitis / chemically induced
  • Endophthalmitis / metabolism*
  • Endophthalmitis / pathology
  • Male
  • Meloxicam
  • Ophthalmic Solutions
  • RNA, Messenger / genetics
  • Rabbits
  • Thiazines / pharmacology*
  • Thiazoles / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cytokines
  • Ophthalmic Solutions
  • RNA, Messenger
  • Thiazines
  • Thiazoles
  • Croton Oil
  • Cyclooxygenase 2
  • Dinoprostone
  • Meloxicam