Single versus combined immunoregulatory approach using PD-1 and CTLA-4 modulators in controlling sepsis

Courtney P. Rudick, David L. Cornell, Devendra K. Agrawal

    Research output: Contribution to journalReview articlepeer-review

    7 Scopus citations


    Introduction: Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved survival in the initial immune response during systemic inflammatory response syndrome, and compensatory anti-inflammatory response, yet is mostly unchanged with 18–30% mortality during the later stage of sepsis despite numerous Phase 3 clinical trials. Areas covered: This review article presents a critical evaluation of the most promising newer studies aimed at improving the immunosuppressive stage of sepsis. Administration of DHEA/AED/AET show promise in improving survival. Blockade of signaling pathways for PD-1/PD-L1/CTLA-4, and partial blockade of TREM-1 signaling, and modification to sTREM-1 and the JAK/STAT pathway are promising methods of restoring host immune response and improving survival. While there has been significant progress, currently no findings have been translated into effective clinical interventions. Expert commentary: Clinical success by immunomodulation with individual immune mediator is encouraging and should progress to evaluating combined methods of immunoregulation. Since most of the animal studies do not reproduce human sepsis, development of better animal models and moving toward human studies for intervention will lead to the most beneficial findings in translational science.

    Original languageEnglish (US)
    Pages (from-to)907-919
    Number of pages13
    JournalExpert Review of Clinical Immunology
    Issue number9
    StatePublished - Sep 2 2017

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology


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