Influence of indomethacin and other anti-inflammatory drugs on mobilization and production of neutrophils: studies with carrageenan-induced inflammation in rats

Abstract

The intrapleural injection of carrageenan in the rat, after a delay of 90 min, resulted in the accumulation of 100 to 300 million neutrophils in the pleural cavity, a 6-fold increase in the numbers of circulating neutrophils and the mobilization of large numbers of neutrophils from bone marrow. Thymidine labeling of bone marrow cells showed that neutrophils underwent a period of maturation (2--3 days) before release into the circulation and accumulation in the pleural cavity. Nonsteroidal anti-inflammatory drugs reduced, in a dose-dependent manner, the accumulation of white cells and fluid. Indomethacin, the most potent of the drugs tested, was equally effective whether given 30 min before or 90 min after carrageenan. This drug had no significant effect on the production or number of white cells in bone marrow, spleen or thymus. In contrast, methotrexate suppressed the inflammatory reaction only after prolonged treatment had produced almost complete depletion of cells in bone marrow and dexamethasone could be given in doses that largely depleted thymus and spleen of their white cells but which had little effect on neutrophil accumulation. It is concluded that neutrophils were mobilized from stores of mature cells in bone marrow and that indomethacin suppressed mobilization of these cells without impairing normal white cell homeostasis.