Administration of recombinant murine CXCL16 protein worsened sepsis-induced mortality
We then studied the functional role of CXCL16 in the model of CLP-induced polymicrobial sepsis. The protein concentrations of CXCL16 were substantially up-regulated in the lung, PLF and blood after CLP (Supplementary Figure 2).The effects of increasing doses (0.5–1.0 μg) of recombinant murine CXCL16 on nonsevere sepsis were firstly assessed in a sublethal model of CLP. We found that treatment with recombinant murine CXCL16 in the absence of sepsis did not affect survival at doses up 1.0 μg in sham control mice. However, supplementation of recombinant murine CXCL16 (0.5–1.0 μg) significantly decreased mice survival compared with the PBS-injected septic mice (Figure 4A). Our subsequent experiments were thus performed in CLP mice using recombinant murine CXCL16 (0.5 μg) immediately after nonsevere CLP.The decrease in survival of septic mice treated with recombinant CXCL16 was related to increased tissue inflammation and organ injury. At 24 hours after nonsevere CLP, inflammation of lung, liver, and kidney was increased (Figure 4B), which was reflected by significantly higher pathology scores in mice treated with recombinant CXCL16 as compared with PBS-treated mice (Figure 4C). Moreover, supplementation of recombinant murine CXCL16 to septic mice significantly increased serum concentrations of ALT, AST, LDH, and creatinine, suggesting a detrimental enhancement of liver, kidney, and cardiac injury (Figure 4D). The decreased survival rate in the mice treated with recombinant murine CXCL16 could not be explained by impaired bacterial clearance, because there was no statistical difference in local or systemic bacterial CFU levels in the septic mice treated with recombinant CXCL16 compared with mice treated with PBS control (Supplementary Figure 3).