CXCL6 was initially isolated from cytokine-stimulated osteosarcoma cells. CXCL6 is structurally most related to CXCL5, and both share 77% identical amino acids. Nevertheless, in spite of the high percentage of amino acid identity, they have differences in expression and cell regulation. CXCL6 has antimicrobial activity and this characteristic is relevant in mucosal infections where endothelial cells are a source for this chemokine. The antimicrobial activity of CXCL6 was compared to CXCL5 and CXCL7, and CXCL6 showed a 90-fold higher activity. CXCL6 antimicrobial activity was inhibited by NaCl and plasma; therefore, CXCL6 may exert its antimicrobial activity in environments where the concentration of plasma and NaCl are low, such as oral cavity mucosa, tonsils, and epithelial cells lining the airways. CXCL6 has been implicated in the pathogenesis of bowel disease, lung cancer, gastrointestinal malignancies, and endometriosis. Also, CXCL6 seems to play a role in the innate immune response in the amniotic fluid; in fact, CXCL6 is present in amniotic fluid, and its concentration increases with gestational age.