Lipoxygenase inhibitor and colchicine as anti-arthritic agents in the rat

The non-steroidal anti-inflammatory agents do not have identical activities on the various pathways of arachidonic acid metabolism. The purpose of this study is to examine and compare the activities of colchicine, an anti-arthritic agent, indomethacin, a known prostaglandin synthesis inhibitor and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor in an experimental model of arthritis. Acute arthritis of the knee was induced in rats by injection of lipopolysaccharide (LPS) into the joints. Arthritis was characterized by an increase in joint diameter (18%), increased synovial weight (34%) and an increase in synovial prostaglandin E (PGE) production (56%). While administration of all of the agents examined abolished LPS-induced joint diameter and synovial weight increase, only indomethacin reduced increased PGE content. NDGA and colchicine had no inhibitory effect on LPS-induced PGE production, and moreover they actually stimulated PGE production when compared to control values. It is concluded that: 1) Among the mediators of the inflammatory process are factors sensitive to colchicine and NDGA which are not PGs. 2) Lipoxygenase products of arachidonic acid including leukotrienes may have an important role in inflammation. 3) Leukotrienes and prostaglandins may act in concert in mediating the inflammatory process.