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. This 8-9 kDa chemokine circulates as a monomer, homodimer, and heterodimer with CXCL4/PF4. Its oligomerization is modulated by interactions with matrix and cell surface glycosaminoglycans (GAGs). Mature porcine CXCL8 shares 82%, 78%, and 65% amino acid (aa) sequence identiity with canine, feline, and human CXCL8. There is no CXCL8 gene counterpart in rodent. N-terminal truncation of CXCL8 by multiple proteases generates a range of shorter forms. The bioactivity of CXCL8 is regulated by these truncations and also by CXCL8 citrullination. 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. These receptors associate into functional homodimers and heterodimers with each other. Through both CXCR1 and CXCR2, CXCL8 promotes neutrophil adhesion to the vascular endothelium and migration to sites of inflammation. It triggers the antimicrobial activation of neutrophils through CXCR1. CXCL8 also binds to Serpin A1/alpha-1 Antitrypsin, and this prevents CXCL8 interaction with CXCR1. CXCL8 is up-regulated in atherosclerotic lesions and other cardiac pathologies where it exacerbates inflammatory tissue damage. In addition, it induces VEGF expression, vascular endothelial cell proliferation, angiogenesis, and tumor cell invasiveness.