Interleukin-8 (IL-8), also known as CXCL8, GCP-1, and NAP-1, is a widely expressed proinflammatory member of the CXC family of chemokines. Near its N-terminus, this 8-9 kDa chemokine contains an ELR motif which is important for its angiogenic properties [1]. IL-8/CXCL8 can associate into a homodimer or a heterodimer with CXCL4/PF4 [2], and it can also interact with matrix and cell surface glycosaminoglycans [3]. Mature human IL-8/CXCL8 shares 65%-69% amino acid (aa) sequence identity with canine, feline, and porcine IL-8/CXCL8 [4]. There is no IL-8/CXCL8 gene counterpart in rodent. N-terminal truncation by multiple proteases generates a range of shorter forms, and an alternative splice form of human IL-8/CXCL8 carries an eleven aa substitution at the C-terminus [5]. The bioactivity of IL-8/CXCL8 is regulated by these truncations, by IL-8/CXCL8 citrullination at Arg5 (N-terminal to the ELR motif) [6], and by the decoy receptor DARC [7]. IL-8/CXCL8 effects are mediated through CXCR1/IL-8 RA, which is also used by CXCL6, and through CXCR2/IL-8 RB, which is used by multiple CXC chemokines [1]. CXCR1 and CXCR2 associate into functional homodimers and heterodimers with each other [8]. Through both CXCR1 and CXC R2, CXCL8 promotes neutrophil adhesion to the vascular endothelium and migration to sites of inflammation [9]. It triggers the antimicrobial activation of neutrophils through CXCR1 [10].
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