Development of Carrageenan Pleurisy in the Rat: Effects of Colchicine on Inhibition of Cell Mobilization

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Abstract
Colchicine produced three effects which modified the acute inflammatory response to carrageenan in the rat pleural cavity: (i) inhibition of neutrophil mobilization and concomitant exudate formation (3 hr); (ii) inhibition of monocyte mobilization (21 hr); and (iii) augmented exudate formation (3 and 21 hr). The 1st effect was related to the intraperitoneal dose of colchicine and occurred only at leukopenic dose levels. This effect could not be produced by intrapleural injection of nonleukopenic doses of colchicine. The second effect, on the other hand, was produced by intraperitoneal leukopenic doses and to a lesser extent by intrapleural administration of nonleukopenic doses of colchicine. Importantly, the normal biphasic exudative response to carrageenan developed fully in the absence of monocytes. The third effect, a dose-dependent augmentation of both exudative phases of carrageenan pleurisy, was produced by low, nonleukopenic, intrapleural doses of colchicine. The augmented exudate was sensitive to prostaglandin synthetase inhibitors but not to anti-inflammatory steroids. Neither neutrophils nor monocytes were responsible for the augmented exudate. Colchicine, injected into the rat hindlimb or pleural and peritoneal cavities did not elicit the mobilization of neutrophils or a pleural effusion. In addition, colchicine did not affect the magnitude, temporal development, or decay of the potent edematogenic action of serotonin in the rat hindlimb. Thus irritancy was not responsible for any of the effects of colchicine.