INTERFERON-GAMMA MODULATES THE EXPRESSION OF NEUTROPHIL-DERIVED CHEMOKINES

Specific cell recruitment to a site of acute inflammation is a crucial event characterized by the elicitation of mainly polymorphonuclear ne utrophils (PMNs). Recently, it has been reported that PMNs can express and secrete chemotactic cytokines or chemokines, including IL-8, MIP- 1 alpha, and MIP-1 beta. Moreover, PMN derived chemokines are regulate d by various soluble mediators, such as dexamethasone, prostaglandin E , classic chemoattractant factors leg, fMLP, C5a, leukotriene B-4), IL -4, and TL-10. In this article we demonstrate that PMNs treated with I FN-gamma, a Th1-derived cytokine, can inhibit early mRNA expression fo r MIP-1 alpha, MIP-1 beta, and IL-8 (up to 8 hours post IFN-gamma addi tion), whileaugmenting their production at 24 hours post IFN-gamma, ad dition. Furthermore, our studies demonstrate that one of the mechanism s for the activity of IFN-gamma in this system is via the autocrine ac tivity of TNF-ol. These data imply that PMN-derived chemokines are reg ulated by not only proinflammatory cytokines, including IL-1 beta and TNF-alpha, but also Th1-and Th2-derived cytokines, including IL-4, IL- 10, and IFN-gamma. The role of these cytokine networks in regulating P MN-derived chemokines may play an important role in leukocyte elicitat ion during the initiation and maintenance of an inflammatory response.