IL-7 and Its Beneficial Role in Sepsis-Induced T Lymphocyte Dysfunction.

ABSTRACT

Sepsis, defined as life-threatening organ dysfunction caused by dysregulated host response to infection, has recently been acknowledged as a worldwide health priority. Sepsis remains the leading cause of mortality in intensive care units and accounts for 6 million deaths every year. Few therapeutic options targeting host immune response in sepsis have demonstrated their efficacy so far. Increasing evidence suggests that a profound immune suppression develops following sepsis, affecting innate and adaptive immune response, of which intensity and duration is associated with increased risk of death and nosocomial infection. Immunostimulant treatments are thus now evaluated in sepsis, and recombinant human IL-7 (rhIL-7) represents a promising candidate. rhIL-7 has been evaluated in several clinical trials in patients with altered lymphocytic responses (HIV infection, hematopoietic stem cell transplantation, and cancer). Recent studies in animal models and in patients' samples ex vivo demonstrated its efficacy in improving sepsis-induced T cell alterations. Finally, the first clinical trial evaluating rhIL-7 in septic shock patients has just been published. This review will discuss the use of rhIL-7 to treat sepsis-induced T cell dysfunction by introducing the pathophysiology of sepsis and sepsis-related lymphocyte alterations before focusing on rhIL-7 and its potential use of as a therapeutic intervention in patients.