Inflammation and superoxide production by macrophages.

Superoxide (.O-2) is demonstrated to participate at the prostaglandin phase swelling (2-4 h) of carrageenan paw edema. Superoxide production is inhibited in vitro by typical anti-inflammatory drugs, but these drugs did not scavenge superoxide which was produced by xanthine oxidase. Phosphate, pyrophosphate, ATP, ADP and sulfate were essential for superoxide production by macrophages. These anions can induce paw swelling and are reported to increase in rheumatic patients. A mixture of macrophages and lymphocytes from BCG sensitized guinea-pigs was cultured for 2 days with SOD or D-mannitol. Nitroblue tetrazolium reduction (formazan formation) was inhibited by these agents, suggesting that the hydroxyl radical (.OH) is necessary for metabolic activation of macrophage. Lympholine-like factor of which production or release is enhanced by hydroxyl radical, activates macrophage. Production of oxygen radicals may increase rapidly by this chain cycle reaction. Possible relations of oxygen radicals to prostaglandin(s) biosyntheses, chemotaxis, lysosomal enzyme release protease participation, were discussed. Endogenous SOD, epinephrine, ceruloplasmin, blood plasma proteins, inflammatory fluid, may modulate the amount of superoxide by their superoxide scavenging capacities.