Sepsis-Induced Immunosuppression: The Role of Co-inhibitory Molecules

Abstract

Sepsis is one of the most common cause of death among hospitalized patients in the intensive care unit (ICU), with current therapeutic options falling short of a comprehensive solution. The condition's pathophysiology is marked by a spectrum of immunological impairments, with a growing consensus that immunosuppression plays a decisive role in the condition's rising morbidity and mortality rates. Extensive preclinical and clinical research has identified the upregulation of several co-inhibitory molecules during sepsis, including Programmed Death-1 (PD-1), Programmed Death Ligand-1 (PD-L1), Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), B and T Lymphocyte Attenuator (BTLA), T Cell Membrane Protein-3 (TIM-3), and Lymphocyte Activation Gene-3 (LAG-3). These molecules, which exert a significant inhibitory effect on T cell function, are believed to contribute to the immunosuppressive state induced by sepsis. The elucidation of the intricate mechanisms by which these molecules induce immunosuppression is essential for devising the most efficacious treatment strategies for sepsis. The burgeoning field of immunotherapy, particularly the blockade of co-inhibitory molecules, represents a significant frontier in sepsis research. This approach holds substantial promise for the future of sepsis therapy, warranting further exploration and clinical investigation to harness its potential fully.