Role of Circulating Lymphocytes in Patients with Sepsis

Abstract

Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

P2Y 12 Receptor Modulates Sepsis-Induced Inflammation

“…Lymphocyte abnormalities have been reported in septic patients, and they were related with the pathophysiology of the disease 31 . P2Y 12 receptor antagonism influenced circulating lymphocyte numbers over platelets and neutrophils.…”

Caspase-8 inhibition represses initial human monocyte activation in septic shock model

“…If this were the case, then the treatment of patients early with caspase-8 inhibitors would both decrease monocyte activation and lead to necroptosis of activating monocytes; cutting SIRS at the source. This would limit the resultant downstream symptoms including lymphocyte apoptosis and immunosuppression [42], which are not counteracted by other treatments. In support of this hypothesis, we detected lower levels of CD40 expression in the surviving monocytes of cultures where necroptosis had been induced with LPS and caspase-8 inhibitors.…”

Proliferation of B-lymphocytes in inflammatory and hematological diseases

“…B-lymphocytes produce immunoglobulins as a response to infection, cytokines as immunoregulatory cells, and as antigens they participate in T-B cooperation [2,3]. Elevated concentrations of cytokines and markers of the B-lymphocyte function are present in various autoimmune diseases (rheumatoid arthritis, systemic lupus, Sjogren's Syndrome) [4,5], as well as in B-cell malignancies [6][7][8], while the role of B-lymphocytes as regulatory immune cells in response to bacterial infections remains the object of many studies.…”

“…Elevated concentrations of cytokines and markers of the B-lymphocyte function are present in various autoimmune diseases (rheumatoid arthritis, systemic lupus, Sjogren's Syndrome) [4,5], as well as in B-cell malignancies [6][7][8], while the role of B-lymphocytes as regulatory immune cells in response to bacterial infections remains the object of many studies. Newer researches both in animal models [6] and in human population [2,3] highlighted individual forms of B-lymphocytes as one of the main regulators of the immune response to infectious agents. The main regulators of B-lymphocytes' function and activity are tumor necrosis factor alpha (TNF-α) superfamily members [9][10][11].…”