Circulating Granzymes are associated with Bloodstream Infection and Death in Febrile Medical Patients

Abstract

Plasma levels of granzymes are specific markers for the activation of cytotoxic T lymphocytes and natural killer (NK) cells but the impact of activation of these cells on the course of bacterial infections is not well understood. We prospectively studied the implications of circulating granzyme A and B (GrA, GrB) levels in febrile, medical and hospitalized patients (n=284), during 3 days after inclusion and related levels to lymphocyte counts, infection, sepsis, culture results, shock and infection-related 28-day mortality. Bloodstream infection occurred in 18% of the patients, 9% died within 28 days. Circulating GrA and GrB levels were elevated, at inclusion, in 98 and 55% of patients. The course of GrB predicted bloodstream infection whereas that of GrA predicted mortality, regardless of relative lymphocytopenia. Our data suggest harmful cytotoxic T and NK cell activation early in bacterial infection-related fever. They also point to an early but different pathogenic role of soluble GrA and GrB when fever is associated with mortality and bloodstream infection, respectively.