Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis

The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base o f tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresp onding to the translation initiation site of rat COX-2 mRNA were prepared. The antisense (AS), sense (S), and "scrambled" (Sc) ODNs were intraperitone ally administered. Arthropathy was evaluated with arthritis score, paw edem a, and histological examination. Expression of COX-1 and -2 protein and mRN A were examined with immunostaining and reverse-transcription polymerase ch ain reaction, respectively. COX-2 AS ODN significantly suppressed induction of arthritis in a dose-dependent manner without severe adverse effects, wh ereas S and Sc ODNs did not show significant inhibitory effects. COX-2 mRNA and protein expression were also suppressed only by COX-2 AS ODN without a ny alteration of COX-I expression. These data suggest that selective inhibi tion of COX-2 with AS ODN may have a therapeutic potency in the treatment o f rheumatoid arthritis. (C) 2000 Academic Press.