Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial
| Autor: | Matthew S. Shotwell, Robin Jeannet, Michel Morre, Thomas Daix, Scott K. Durum, Bruno François, Anne Gregoire, Andrew H. Walton, Guillaume Monneret, Edward R. Sherwood, Richard S. Hotchkiss, Jacqueline Unsinger, Jane Blood, Gail A. Mayo, Teresa M. Blood, Thomas Rimmelé |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell Immunology lcsh:Medicine Lymphocyte proliferation Sepsis 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans Lymphocytes business.industry Septic shock Interleukin-7 lcsh:R General Medicine Acquired immune system medicine.disease Shock Septic 030104 developmental biology Cytokine medicine.anatomical_structure Immunization Clinical Medicine business Cytokine storm 030215 immunology |
| Zdroj: | JCI Insight, Vol 3, Iss 5 (2018) |
| ISSN: | 2379-3708 |
| Popis: | BACKGROUND. A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS. We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 weeks. Primary aims were to determine the safety of CYT107 in sepsis and its ability to reverse lymphopenia. RESULTS. CYT107 was well tolerated without evidence of inducing cytokine storm or worsening inflammation or organ dysfunction. CYT107 caused a 3- to 4-fold increase in absolute lymphocyte counts and in circulating CD4+ and CD8+ T cells that persisted for weeks after drug administration. CYT107 also increased T cell proliferation and activation. CONCLUSIONS. This is the first trial of an immunoadjuvant therapy targeting defects in adaptive immunity in patients with sepsis. CYT107 reversed the marked loss of CD4+ and CD8+ immune effector cells, a hallmark of sepsis and a likely key mechanism in its morbidity and mortality. CYT107 represents a potential new way forward in the treatment of patients with sepsis by restoring adaptive immunity. Such immune-based therapy should be broadly protective against diverse pathogens including multidrug resistant bacteria that preferentially target patients with impaired immunity. TRIAL REGISTRATION. Trials registered at clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02640807","term_id":"NCT02640807"}}NCT02640807 and {"type":"clinical-trial","attrs":{"text":"NCT02797431","term_id":"NCT02797431"}}NCT02797431. FUNDING. Revimmune, NIH National Institute of General Medical Sciences GM44118. |
| Databáze: | OpenAIRE |
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