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).