Effects of heme oxygenase-1 inducers on established rat adjuvant arthritis.

Heme oxygenase-1 (HO-1) activity can inhibit inflammatory and immune responses. We have examined the influence of HO-1 induction on the established rat adjuvant arthritis model of chronic inflammation. Therapeutic administration of cobalt protoporphyrin IX (CoPP; 5 mg/kg/day i.p.) from day 17 to 23 significantly reduced the inflammatory response, with partial inhibition of hind paw edema and the production of some inflammatory mediators such as nitric oxide metabolites and tumor necrosis factor-alpha, although joint erosion was observed. Hemin administration (26 mg/kg/day i.p.) during the same time period was ineffective on these parameters. Western blot analysis of hind paw homogenates revealed a weaker induction of HO-1 by this compound in comparison with CoPP. Our data indicate that pharmacological HO-1 induction after the establishment of adjuvant arthritis partially reduced the inflammatory response but it was not sufficient to control joint erosion in our experimental conditions.