Abstract
Chemokine CXC motif ligand 16 (CXCL16) is a multifaceted chemokine that
has been shown to participate in a variety of inflammatory diseases. The
role of CXCL16 in the immunopathology of sepsis remains unidentified. In
this study, human patients with sepsis and healthy controls were used to
obtain blood for in vitro studies, and female C57BL/6J mice were taken
for in vivo studies. The effects of recombinant CXCL16 protein or
anti-CXCL16 monoclonal antibody on sepsis were evaluated in a murine
model of cecal ligation and puncture (CLP)–induced polymicrobial
sepsis. On admission, human patients with sepsis had significantly
higher soluble levels of serum CXCL16 than healthy controls. Soluble
CXCL16 remained significantly elevated in septic patients from day 0 to
7. Admission levels of soluble CXCL16 were positively correlated disease
severity and the serum levels of other inflammatory cytokines and
chemokines. Furthermore, nonsurvivors displayed significantly higher
admission levels of soluble CXCL16 compared with survivors of septic
patients. Soluble CXCL16 levels revealed significant prognostic value
for 28-day mortality, and CXCL16 was found to be an independent
predictor of 28-day mortality in septic patients. In CLP-induced
nonsevere sepsis, administration with recombinant CXCL16 increased
mortality and tissue injury. Conversely, neutralizing CXCL16 by
anti-CXCL16 monoclonal antibody decreased mortality and tissue injury in
CLP-induced severe sepsis. However, CXCL16 did not affect the ability of
these mice to clear bacteria in CLP. Taken together, CXCL16 could be
linked to sepsis not only as a new marker of prognosis, but also as a
potential target for therapeutic intervention.