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L. Vega, J. R. Cruz, L. M. Baiza-Durán, J. Gonzalez, R. Tornero-Montaño, J. D. Quintana-Hau; Effects of Meloxicam on COX-2 Expression, PGE2 Release, and Cytokine Expression in an Experimental Model of Rabbit Acute Ocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5215.
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The aim of this study was to investigate the effects of an ophthalmic formulation of meloxicam on COX-2 activity and expression, on inflammation-related cytokines expression (IL-1ß, IL-6, IL-10, IFNγ and TNFα), and on inflammation in an experimental animal model of acute ocular inflammation and to compare the efficacy of the meloxicam ophthalmic formulation to the effects of a typical commercial diclofenac ophthalmic formulation.
Ocular inflammation was induced in New Zealand rabbit with topical application of croton oil at 3% for 3 h. Every 4 h after inflammation induction, two drops of ophthalmic solutions of meloxicam at 0.03%, sodium diclofenac at 0.1%, or placebo (only the vehicle of the ophthalmic solutions) were administered. At different end point times, animals were sacrificed by CO2 inhalation and conjunctiva, cornea, aqueous and vitreum humor were obtained. Expression of COX-2 and cytokines mRNA in cornea and conjunctiva were measured by semi-quantitative RT-PCR using 18s expression as a control. PGE2 levels in ocular tissues were measured by EIA as a measure of proinflammatory activity of COX-2.
Basal expression of COX-2 mRNA was 2.7 times higher in cornea than in conjunctiva, and croton oil treatment after 3 h up-regulated COX 2-mRNA in cornea and conjunctiva (2 fold and 3 fold increase, respectively). PGE2 levels in aqueous humor changed in the same manner as COX-2 expression varied. In inflammated eyes, meloxicam treatment down-regulated COX-2 expression and activity (mRNA and PGE2 levels, respectively) in a time dependent manner, and reduced inflammation at 72 h of treatment. Diclofenac could not down-regulate COX-2 mRNA or PGE2 to basal levels after 7 days of treatment. Regarding the regulation of the immunologic profile, croton oil up-regulated IL-1ß, IL-6, IFNγ and TNFα in conjunctiva while IL-10 was not modified. In cornea, croton oil up-regulated TNFα and IL-1b, while IL-10 was not modified and IFNγ and IL-6 were not detected. Meloxicam treatment in inflammated eyes down-regulated IL-6 and IFNγ in conjunctiva , and IL-1ß and TNF-α in both cornea and conjunctiva.
Expression of COX-2 mRNA in cornea and conjunctiva parallels with the levels of PGE2 present in aqueous humor and correlate with the corneal and conjunctival inflammation. Also, meloxicam treatment was more efficient than diclofenac in down-regulating the expression and activity of COX-2, thus reducing inflammation in a shorter time than diclofenac.
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