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

OBJECTIVE AND DESIGN

This study examined whether serum levels of cytokines, IL-1beta and TNFalpha 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 mg/kg, p.o.), a type-4 phosphodiesterase (PDE4) inhibitor, alone or in combination.

MATERIALS AND METHODS

Female Wistar rats were used. Freund's complete adjuvant (FCA) was used to induce arthritis. The increment in contralateral hind paw volume (the secondary lesion) was determined by plethysmometry and the serum cytokines were measured by ELISA.

RESULTS

In control rats, the serum IL-1beta and TNFalpha levels were greatly elevated on the very first day i.e. 5 h after FCA, and thereupon a progressive decrease in IL-1beta but not TNFalpha was observed until day 30. The secondary arthritic lesion began to increase on day 14 (125+/-26 microl), and attained its peak (330+/-79 microl) on day 21 post-adjuvant injection. The peak arthritic lesion was significantly (p<0.001) less in rats that received nabumetone and pentoxifylline, alone or in combination (20+/-8, 41+/-15 and 65+/-10 microL, respectively). When serum cytokine levels were analysed on day 20 postadjuvant injection, rats treated with pentoxifylline or in association with nabumetone, but not nabumetone alone showed significantly lowered levels of serum TNFalpha. Unlike TNFalpha, serum IL-1beta did not vary significantly.

CONCLUSIONS

The drugs nabumetone and pentoxifylline although appearing to produce differential effects on serum cytokine levels, seem to be equally efficacious in attentuating the progression of FCA-induced arthritis. Serum cytokine levels may not accurately reflect the treatment efficacy.