Effects of antimalarial drugs on interleukin 1-induced cartilage proteoglycan degradation in-vitro

Abstract

Previous studies having shown that chloroquine and hydroxychloroquine could reduce interleukin 1 (IL-1)-induced cartilage degradation in-vitro, the effects of a range of antimalarial drugs on the cartilage proteoglycan degrading actions of porcine leucocyte (pI 4.8) alpha-interleukin 1 (syn. catabolin) have been examined using the standard bovine nasal cartilage culture system. The anti-IL-1 effects in this system were specific to several aminoquinoline and aminoacridine analogues having a side chain with a tertiary amino group similar to that of chloroquine. Aminoquinoline compounds devoid of this side chain and the tertiary amino, as well as pyrimidines or biguanides with antimalarial activity were without effect. Mefloquine, the most potent of the compounds active against porcine alpha-IL-1, was only equipotent with chloroquine and its hydroxyanalogue against human recombinant alpha-IL-1. This suggests that there may be subtle differences in the receptors for these drugs and interleukins in bovine cartilage. The results provide further evidence for the specificity and utility of antimalarial drugs in the treatment of chronic inflammatory conditions, especially in relation to actions on IL-1.