Sepsis remains a major cause of morbidity and mortality in most intensive care units. Protracted
sepsis can evolve into a state of profound immunosuppression characterized by
secondary infections, frequently with opportunistic-type pathogens.
Immunoadjuvant therapy is currently being evaluated as a novel treatment for patients with
sepsis. Two of the most promising
immunoadjuvants are
interleukin-7 (IL-7) and anti-programmed cell death 1 antibody (anti-PD-1). Both
IL-7 and anti-PD-1 have been reported to boost host immunity and improve outcomes in patients with
viral infections and
cancer. The purpose of this study was to define the immunological mechanisms of action of
IL-7 and anti-PD-1 in the two-hit
sepsis model of cecal
ligation and
puncture followed by Candida albicans. In addition, we examined whether combined treatment with
IL-7 and anti-PD-1 provided any additive beneficial effects in reversing immune dysfunction. The present findings demonstrated that
IL-7 and anti-PD-1 had differing effects on innate and adaptive immune functions. Compared with anti-PD-1,
IL-7 increased lymphocyte proliferation; expression of lymphocyte adhesion molecules,
lymphocyte function-associated antigen 1, and
very late antigen-4;
interferon-γ production; and CD28 expression on splenic CD8 T cells. In contrast, anti-PD-1 seemed to have a greater effect on major histocompatibility complex class II expression on splenic macrophages and dendritic cells than
IL-7. Combined treatment with
IL-7 and anti-PD-1 produced additive effects on CD28 expression, lymphocyte proliferation, and splenic secretion of
interferon-γ. In conclusion, the present study shows differences in immunomodulatory actions between
IL-7 and anti-PD-1 and provides a potential rationale for combining
IL-7 and anti-PD-1 in the
therapy of
sepsis.