Hemorrhagic shock (HS) followed by resuscitation has been shown to initiate a series of events, including local cytokine production and PMN accumulation. To determine whether PMN are involved in the regulation of IL-6 expression in the liver or lungs, IL-6 mRNA levels were measured in rats made neutropenic by vinblastine pretreatment prior to HS. IL-6 mRNA levels were determined at 4 or 24 h following resuscitation from shock. Vinblastine alone in normal rats or sham-treated rats had no effect at 4 or 24 h. Vinblastine pretreatment had no effect on the HS-induced increase in IL-6 mRNA at 4 h but dramatically increased levels in both liver and lung at 24 h. Peripheral PMN counts were reduced by 95% in all vinblastine-treated animals. Similar changes seen in CD14 mRNA expression indicate that these effects are not limited to IL-6. These data show that normal PMN levels are not needed for induction of IL-6 and CD14 in HS, and suggest that PMN accumulation down-regulates the expression of these genes.