IMMUNOSUPPRESSION IN SEPSIS DETECTED BY REACTIVATION OF LATENT VIRUSES

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): Physicians are increasingly confronting the difficult problem of management of patients with sepsis. A current debate in the field is the degree to which sepsis is primarily a disorder due to tissue injury from uncontrolled inflammation versus a disorder due to immunosuppression and failure to control invading pathogens. Recent evidence indicates that some patients with sepsis enter a prolonged anti-inflammatory immunosuppressive phase. This immunosuppressive phase is characterized by inability of the patient to clear their initial infection and development of secondary hospital-acquired infections. Another feature of sepsis consistent with impaired immunity is reactivation of latent viruses. The working hypothesis of the present proposal is that sepsis results in loss of immunity manifested by a variety of measures including decreased absolute lymphocyte counts, decreased CD4, CD8, and NK cell counts resulting in viral reactivation. At the conclusion of the project, a method to identify when patients enter the immunosuppressive phase of sepsis will have been identified and key factors that might contribute to sepsis pathogenesis will have been discovered.