Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial

• DOI: 10.1172/jci.insight.98960
• Publication Date: 2018-03-07T16:02:53Z
• Authors: Bruno Francois; Robin Jeannet; Thomas Daix; Andrew H. Walton; Matthew S. Shotwell; Jacqueline Unsinger; Guillaume Monneret; Thomas Rimmelé; Teresa Blood; Michel Morre; Anne Gregoire; Gail A. Mayo; Jane Blood; Scott K. Durum; Edward R. Sherwood; Richard S. Hotchkiss
• Keywords: Cytokine Storm; Cellular immunity; Organ dysfunction

A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion CD4+ CD8+ T cells. Interleukin-7 (IL-7) an antiapoptotic common γ-chain cytokine that essential for lymphocyte proliferation survival. Clinical trials IL-7 in over 390 oncologic lymphopenic patients showed was safe, invariably increased counts, improved immunity.We conducted a prospective, randomized, double-blind, placebo-controlled trial recombinant human (CYT107) with septic shock severe lymphopenia. Twenty-seven at academic sites France the United States received CYT107 or placebo 4 weeks. Primary aims were to determine safety its ability reverse lymphopenia.CYT107 well tolerated without evidence inducing storm worsening inflammation organ dysfunction. caused 3- 4-fold increase absolute counts circulating cells persisted weeks after drug administration. also cell activation.This first immunoadjuvant therapy targeting defects adaptive immunity sepsis. reversed marked loss immune effector cells, hallmark likely key mechanism morbidity mortality. represents potential new way forward treatment by restoring immunity. Such immune-based should be broadly protective against diverse pathogens including multidrug resistant bacteria preferentially target impaired immunity.Trials registered clinicaltrials.gov: NCT02640807 NCT02797431.Revimmune, NIH National Institute General Medical Sciences GM44118.