Mechanisms of Zymosan Induced IL-8 Generation in Vivo

Abstract

Acute peritonitis in the rabbit induced by intraperitoneal injection of zymosan is characterised by the sequential generation of at least three neutrophil chemoattractants (1). An initial phase of C5a generation (0-2 hours) is followed (2 hours onwards) by the appearance of two structurally related chemoattractant cytokines, rabbit IL-8 and rabbit MGSA (2). The time course of cytokine generation is similar to that of neutrophil accumulation, and phagocytosing neutrophils release IL-8 in vitro. We have therefore investigated whether the infiltrating neutrophils are the source of the IL-8 observed in the cavity at 6 hours. Depletion of circulating neutrophils (>98%) did not inhibit the generation of inflammatory mediators in the peritoneal cavity measured by both in vivo bioassay in skin and using a rabbit IL-8 specific RIA. In addition, HPLC separation of the mediators in exudate from depleted animals revealed that the inflammatory activity comprised both IL-8 and MGSA. Thus, it appears that infiltrating neutrophils are not necessary for production of these cytokines in this model, implicating other cells such as macrophages or mesothelial cells as the source.