A comparison of the effect of benzopyrones and other drugs with anti-inflammatory properties on acid and neutral protease activity levels in various tissues after thermal injury.

Generally, the benzopyrones enhanced acid protease activity levels in the oedema fluid and the extracellular compartment of the skin. This is the region where thermal injury has its greatest impact. The proteolysis induced by the drugs in this region represents a means of rapidly reducing some of the derangements which the thermal injury has caused. Levamisole also enhanced acid protease activity levels in the serum and extracellular compartment of the skin 6 hours after thermal injury, while Reparil had the same effect at 24 hours. Generally the benzopyrones had little or no effect on neutral protease levels, while levamisole and Reparil caused their depression. The later effects could possibly be attributed to serum deactivation or to inhibition of their release. The enzyme enhancing activity of these drugs has been shown to correlate remarkably well with their oedema reducing ability. Generally, those which increased enzyme activity levels the most were the most effective in reducing the oedema. The cells upon which the drugs exert their effects in thermal oedema mainly seem to be the macrophages; the fibroblasts seem to be of secondary importance. This is to be contrasted with their action in the initial stages of lymphoedema where they are believed to stimulate the neutrophils. The net result of the proteolysis is many small fragments which can rapidly leave the injured tissue thus releasing the oedema fluid.