Adjuvant-induced arthritis and drug-metabolizing enzymes

Rats given a single intradermal injection into the foot pad of 0.50 mg Mycobacterium butyricum, suspended in 0.1 ml of liquid paraffin, developed arthritis after a latent period of about 8 days. However, a decline in the activity of hepatic aminopyrine demethylase and the level of cytochrome P-450 occurred before the development of arthritis. Rats given the adjuvant preparation by the intraperitoneal route showed also a decreased activity of aminopyrine demethylase. An inverse correlation was found between the level of α₂-globulin and aminopyrine demethylase activity. Rats in which arthritis was induced by Mycoplasma arthritidus also showed a reduced activity of aminopyrine demethylase. The reduction of aminopyrine demethylase activity in adjuvant-treated rats was not caused by anorexia, neither could it be shown to be caused by a circulating hormonal factor. However, it was noted that the serum from many of the arthritic rats was greenish in colour and this might have been caused by the breakdown of certain haem compounds. The haem saturation of hepatic tryptophan oxidase was much less in adjuvant-induced arthritic rats than in controls. These results suggest a failure in haem biosynthesis and/or an accelerated breakdown of existing haem.