INDUCTION OF INTERLEUKIN-8 SYNTHESIS FROM MONOCYTES BY HUMAN C5A ANAPHYLATOXIN

Interleukin-8 (IL-8) is an important mediator of inflammation and has been shown to be a potent chemotactic/cell activator for polymorphonuc lear neutrophils (PMNs), T lymphocytes, and basophils. Cellular source s of IL-8 include monocytes, PMNs, endothelial cells, epithelial cells , and keratinocytes when stimulated by factors such as lipopolysacchar ide, IL-1 and tumor necrosis factor-alpha. This report demonstrates th at C5a, in addition to being a direct mediator of inflammation, can in duce both IL-8 synthesis and high levels of release from monocytes. Na tural human C5a and a synthetic C-terminal analogue peptide of C5a eac h induced IL-8 synthesis and release from CD14(+) human peripheral blo od mononuclear cells. Antigenic reactivity based on enzyme-linked immu nosorbent assay gave evidence that IL-8 was present in the culture sup ernatants of stimulated peripheral blood mononuclear cells. Proof that supernatant levels of IL-8 attain biologically significant quantities was provided by human PMN chemotaxis assays. The quantity of IL-8 rec overed from C5a-activated monocytes in peripheral blood mononuclear ce lls is up to 1,000-fold greater than that released from comparable num bers of PMNs under similar conditions. Therefore, IL-8 released from C 5a-activated monocytes may play a significant role in expanding and pr olonging cellular infiltration and activation at sites of infection, i nflammation, or tissue injury. This observation suggests an important humoral amplification loop for inflammatory events involving both comp lement activation and cytokine release.