Pharmacology of interleukin-1-induced neutrophil migration

Neutrophil (PMN) accumulation induced by interleukin-1 beta (IL-1 beta, 5-20 ng) into the mouse air pouch was inhibited in a dose-dependent manner (2-200 micrograms) by concomitant injection of IL-1 receptor antagonist (IL-1RA). Similarly, co-administration of the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) resulted in a reduction of the number of migrated PMN but only at the highest dose tested (200 micrograms). Although IL-1RA does not select between the two types of receptors so far described for IL-1, the effectiveness of alpha-MSH suggests that this property of the cytokine may occur through IL-1 type I receptor. This observation was confirmed by using a specific monoclonal antibody (mAb) raised against this receptor type, and which strongly inhibited (87%) IL-1-induced PMN recruitment.