Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis.

Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (gzm) are proteases mainly found in cytotoxic lymphocytes, that not only have a role in target cell death, but also as mediators of infection and inflammation. We here sought to analyse the intracellular expression of gzm A, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected ICU patients and 32 healthy controls. Additionally, we measured gzmA and B plasma levels. Both groups of patients presented decreased percentage of NK cells expressing gzmA, gzmB and gzmM relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing gzmB compared to controls. Expression of gzmK remained relatively unaltered between groups. Extracellular levels of gzmB were increased in non-infected ICU patients relative to sepsis patients and to healthy controls. Our results show differential alterations in intracellular expression of gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the gzm.