Roles of PD-1 and PD-l1 receptors in the development of systemic inflammatory response and immunoadjuvant therapy

The modern view of systemic inflammatory response revolves around the fact that the key pathophysiological link is immunosuppression rather than the initial hyperinflammatory phase as previously supposed. Immunosuppression in critically induced systemic inflammatory response syndrome is associated with increased susceptibility of patients to secondary nosocomial infections and increased probability of progression to multiple organ failure. The role of programmed cell death protein 1 (PD-1) has been investigated in the context of systemic inflammatory response from the standpoint of its participation in the development of immunosuppression. One of the mechanisms of immunosuppression is the exhaustion of T-cells mediated by inhibitory PD-1 receptors. In the body, the PD-1/programmed death-ligand 1 (PD-L1) pathway regulates autoimmunity, tumour immunity, transplant immunity, allergies and immunopathology. This review summarises the results of experimental studies demonstrating that blocking the interaction of PD-1 with its PD-L1 ligand recovers T-cell dysfunction and improves survival rates in animal models of sepsis. Moreover, a clinical case of the use of anti-PD-1 therapy that led to improvement in the status of a critically ill patient is described. Undesirable side effects of this therapeutic approach are also evaluated. Meanwhile, immune checkpoint inhibitors have been introduced into clinical practice to treat certain forms of cancer. Increased expression of PD-1 receptors in systemic inflammatory response syndrome is may thus be a prognostic marker.