Evaluation of immunosuppressive potential of cryogenine using developing and established adjuvant arthritis in rats.
Both developing (Days --1-+12 relative to inoculation) and established (Days +18-+29) stages of Mycobacterium butyricum adjuvant-induced polyarthritis in rats were treated orally with cryogenine (100 mg/kg/day), a prototype anti-inflammatory (phenylbutazone, 100 mg/kg/day), or a prototype immunosuppressive (cyclophosphamide, 6 mg/kg/day). During developing adjuvant arthritis, cryogenine and phenylbutazone significantly reduced the nonimmune-mediated inflammation in the inoculated hindpaw. Neither cryogenine nor phenylbutazone provided protection against the development of the delayed-onset, immune-mediated inflammation and the reduction in growth rate seen after Day +12 in unmedicated rats. Cyclophosphamide failed to reduce the nonimmune-mediated inflammation, but it provided significant protection against both the delayed-onset, immune-mediated inflammation and the reduced growth rate. During established adjuvant arthritis, cryogenine and phenylbutazone were effective against the established inflammation, while cyclophosphamide was ineffective. These results confirm the known anti-inflammatory and immunosuppressive activities of phenylbutazone and cyclophosphamide, respectively, and indicate that cryogenine lacks immunosuppressive capability at the effective anti-inflammatory dosage level used.