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


CONCLUSIONS
Meloxicam treatment was more efficient than diclofenac in downregulating the expression and activity of COX-2, reducing inflammation, and modifying the inflammatory-related cytokines.
Cruz
R
R
Sección Externa de Toxicología, CINVESTAV, Av. IPN 2508, San Pedro Zacatenco, Mexico DF, 07360, Mexico.
Quintana-Hau
J D
JD
González
J R
JR
Tornero-Montaño
R
R
Baiza-Durán
L M
LM
Vega
L
L
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001082:Aqueous Humor / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003436:Croton Oil; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D009877:Endophthalmitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000077239:Meloxicam; D009883:Ophthalmic Solutions; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D013843:Thiazines; D013844:Thiazoles; D003436:Croton Oil; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000077239:Meloxicam