Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions

Abstract

Leukocyte infiltration is a hallmark of inflammation. Knowledge on molecular mechanisms of leukocyte infiltration has advanced rapidly due to the recent elucidation of structures and functions of adhesion molecules and chemokines. Since the discovery of interleukin-8 (IL-8), a prototype of CXC chemokines, in 1987 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), a prototype of chemotactic cytokines (CC) chemokines, in 1989, more than 30 members of chemokines have been identified so far. Evidence is accumulating that these chemokines exert overlapping but distinct actions on specific types of leukocytes in vitro through interacting with their specific G-protein-coupled receptors with seven transmembrane domains. However, redundancy at receptor levels has frequently hindered the clarification on the precise physiological or pathophysiological roles of chemokines. Here, we describe the pathophysiological roles of IL-8 and MCAF/MCP-1 in several animal models of neutrophil- and macrophage-mediated inflammation, respectively, by focusing on our recent work using neutralizing antibodies to these chemokines. We discuss further potential roles of these chemokines in T-lymphocyte-mediated immune responses.