IL-8 contributes to postoperative adhesion formation through the crosstalk of neutrophils and mesothelial cells.

Postoperative adhesions (PA) remain an untreatable complication of abdominal surgery. In this study, we analyzed the role of interleukin-8 (IL-8) in the formation of PA using human cells in vitro and cynomolgus monkeys in vivo, as rodents lack the IL-8 gene. In an in vitro chemotaxis assay, recombinant IL-8 attracted more human neutrophils than its functional homologue, CXCL1, reflecting the dual engagement of CXCR1/2. In the human mesothelial cell line MeT-5A, IL-8 induced TNF-α secretion, which was abolished by the anti-IL-8 antibody AMY109. Conversely, TNF-α dose-dependently upregulated IL-8, supporting a reciprocal amplification loop. Although IL-8 did not directly alter the expression of fibrotic genes in neutrophils or mesothelial cells, TNF-α upregulated TGFB1 mRNA in neutrophils, linking early IL-8/TNF-α signaling to profibrotic cascades. In monkey PA models, IL-8 in the injured abdominal wall was upregulated at 6 h post-surgery. Prophylactic AMY109 (10 mg/kg, i.v.) reduced the abdominal-wall adhesion score (P < 0.05) and tended to lower uterine adhesions (P = 0.0907). These findings suggest that IL-8 orchestrates neutrophil recruitment and crosstalk between neutrophils and mesothelial cells, amplifying inflammation and fibrosis, and that IL-8 blockade effectively attenuates PA formation. Targeting IL-8 therefore represents a promising pharmacological strategy to prevent PA.