has been shown to participate in the control of viral infections and cancer. Here we hypothesized that interleukin-17D
may play a potential role in sepsis
Prospective randomized animal investigation and in vitro human blood studies.
Research laboratory from a university hospital.
Female C57BL/6J mice, sepsis
patients by Sepsis
-3 definitions, ICU patient controls, and healthy individuals.
Serum concentrations of interleukin-17D
were measured and analyzed in human sepsis
patients, patient controls, and healthy individuals. The contribution of interleukin-17D
-related survival, bacterial burden, and organ injury was assessed in a murine model of cecal ligation and puncture–induced polymicrobial sepsis
by the use of anti–interleukin-17D
antibody and recombinant interleukin-17D
protein. The effects of interleukin-17D
on bacterial phagocytosis
by macrophages were also investigated using in vitro cell models.
Measurements and Main Results:
On the day of ICU admission (day 0), septic patients had significantly higher serum concentrations of interleukin-17D
than patient controls and healthy individuals. Serum interleukin-17D
levels remained significantly elevated in septic patients from ICU admission to day 3 and correlated with Sequential (Sepsis
-related) Organ Failure Assessment scores and documented bacteremia on day 0. Furthermore, nonsurvivors of septic patients displayed significantly higher interleukin-17D
levels compared with survivors of septic patients on days 0 and 1 of ICU admission. In animal models of sepsis
, treatment with anti–interleukin-17D
antibody protected mice from cecal ligation and puncture–induced severe sepsis
, which was associated with improved bacterial clearance and organ injury. Conversely, administration of recombinant interleukin-17D
protein aggravated cecal ligation and puncture–induced nonsevere sepsis
. Furthermore, we found that interleukin-17D
impaired bacterial phagocytosis
by macrophages. Phagocytosis
inhibition by interleukin-17D
involved its ability to down-regulate the activation of nuclear factor-κB signaling pathway in macrophages upon bacterial infection
This study indicates a previously undescribed role of interleukin-17D
and identifies a new target for antisepsis treatment.