Effects of pentoxifylline and nabumetone on the serum levels of IL-1 beta and TNF alpha in rats with adjuvant arthritis

Objective and Design: This study examined whether serum levels of cytokines , IL-1 beta and TNF alpha were elevated in rats with adjuvant arthritis in relation to disease progression, and if so, to verify the treatment effects of nabumetone (20 mg/kg, p.o.), a COX-2 inhibitor and pentoxifylline (20 m g/kg, p.o.), a type-4 phosphodiesterase (PDE4) inhibitor, alone or in combi nation. Materials and Methods: Female Wistar rats were used. Freund's complete adju vant (FCA) was used to induce arthritis. The increment in contralateral hin d paw volume (the secondary lesion) was determined by plethysmometry and th e serum cytokines were measured by ELISA. Results: In control rats, the serum IL-1 beta and TNF alpha levels were gre atly elevated on the very first day i.e. 5 h after FCA, and thereupon a pro gressive decrease in IL-1 beta but not TNF alpha was observed until day 30. The secondary arthritic lesion began to increase on day 14 (125 +/- 26 mu l), and attained its peak (330 +/- 79 mu l) on day 21 post-adjuvant injecti on. The peak arthritic lesion was significantly (p <0.001) less in rats tha t received nabumetone and pentoxifylline, alone or in combination (20 +/- 8 , 41 +/- 15 and 65 +/- 10 mu L, respectively). When serum cytokine levels w ere analysed on day 20 post-adjuvant injection, rats treated with pentoxify lline or in association with nabumetone, but not nabumetone alone showed si gnificantly lowered levels of serum TNF alpha. Unlike TNF alpha, serum IL-1 beta did not vary significantly. Conclusions: The drugs nabumetone and pentoxifylline although appearing to produce differential effects on serum cytokine levels, seem to be equally e fficacious in attentuating the progression of FCA-induced arthritis. Serum cytokine levels may not accurately reflect the treatment efficacy.