Increase in body temperature during carrageenin-induced paw oedema in the rat. Effect of non-steroid anti-inflammatory substances and essential fatty acid deficiency

Abstract

Hyperthermia, caused by carrageenin induced paw oedema, is supposed to be mediated by prostaglandins. The influence of prostaglandins formed in the inflamed area and those synthesized in the central nervous system has been studied. A comparison was made between normal animals and animals which lack the precursors of prostaglandin synthesis (essential fatty acid (EFA) deficient animals). Subcutaneous administration of indomethacin prevents or abolishes the temperature increase. The effect of EFA deficiency on the level of fatty acids in the brain was measured. A decrease in the amount of arachidonic acid was observed. The EFA deficient rats showed a smaller increase in body temperature during the carrageenin-induced oedema than normal animals. This increase could also be prevented by indomethacin. Paracetamol (s.c.) caused a dose-dependent decrease in body temperature in both carrageenin and non-carrageenin treated normal and EFA deficient rats. Intraventricular administration of indomethacin diminished the rise in body temperature in normal animals. It is concluded that the temperature increase induced by a peripheral inflammation is at least in part dependent upon a centrally mediated effect. Inhibition of prostaglandin synthesis leads to a diminished response. It is shown that local PG-synthesis and PG-mediated hyperthermia are two independent processes, both triggered by the inflammatory reaction.