Effect of indomethacin on generation of chemotactic activity in inflammatory exudates induced by carrageenan.

Chemotactic activity of protein origin was demonstrated in carrageenan-induced pleural exudates by the chemotactic response of neutrophils in the modified Boyden chamber. The activity was partly neutralized by monospecific antisera to complement component 5 and was destroyed by trypsin and chymotrypsin treatment but it differed from that in rat serum or plasma in that it was stable for 30 min at 56 degrees C. Indomethacin (5 mg/kg i.v.) reduced equally protein content (56%) and total chemotactic activity (58%); i.e., chemotactic activity/mg of exudate protein was unchanged. Intrapleural injection of autologous or homologous serum also induced an infiltration of neutrophils; the protein content of the pleural fluid decreased by 60-70% in 4 h, whereas with carrageenan there was a progressive increase in exudate protein. When serum was injected in two doses to maintain protein levels comparable to those found following carrageenan injection, the number of neutrophils in the exudates was also comparable. In contrast to carrageenan, the response to serum was not inhibited by indomethacin. From these and other data we suggest that the exudate chemotactic activity is generated from plasma protein and that indomethacin acts primarily to reduce extravasation of plasma and consequently generation of chemotactic activity.