Morphine-induced enhancement in the granulocyte response to thioglycollate administration in the rat

The present study determined the pharmacological effects of acute morphine treatment on the granulocyte phase of the peritoneal inflammatory response to thioglycollate (TG) in rats. Dual-color flow cytometry using anti-CD11b/c-PE mAb in combination with HIS48-FITC mAb allowed for the determination of morphine's effects on 4 inflammatory cell subsets: CD11b /c(+)HIS48(med) granulocytes; CD11b /c(hi)HIS48(neg/lo) activated macrophages; CD11b/c(-)HIS48(-) lymphocytes; and CD11b/c(+)HIS48(hi) cells (a monocyte/macrophage and granulocyte subset). Morphine produced a dose-dependent increase in a select subset of inflammatory peritoneal cells, the CD11b/c(+)HIS48(med) granulocytes. The effect of morphine was time-dependent, with significant effects first apparent at 4 hr after TG, but the administration of morphine 1 hr before or simultaneously with TG produced a similar increase in CD11b/c(+)HIS48(med) granulocytes. Naltrexone completely antagonized the morphine-induced increase in CD11b/c(+)HIS48(med) granulocytes. Collectively, these studies show that a single administration of morphine produces a time-dependent, dose-dependent, opioid receptor-mediated enhancement in the peritoneal granulocyte response to TG.