Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial

作者：Thomas Daix, Armelle Mathonnet, Scott C. Brakenridge, Pierre‐François Dequin, Jean‐Paul Mira, Frederique Berbille, Michel Morre, Robin Jeannet, Teresa M. Blood, Jacqueline Unsinger, Jane Blood, Andrew H. Walton, Lyle L. Moldawer, Richard S. Hotchkiss, Bruno François · 发表于：Annals of Intensive Care · 年份：2023 · DOI：10.1186/s13613-023-01109-w · 被引用次数：85 · 研究领域：Sepsis Diagnosis and Treatment、Immune Response and Inflammation、Immune cells in cancer

Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days. Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5–8 h after drug administration. Intravenous administration of CYT107 resulted in a two–threefold increase in absolute lymphocyte counts (including in both CD4+ and CD8+ T cells (all p < 0.05)) compared to placebo. This increase was similar to that seen with intramuscular administration of CYT107, was maintained throughout follow-up, reversed severe lymphopenia and was associated with increase in organ support free days (OSFD). However, intravenous CYT107 produced an approximately 100-fold increase in CYT107 blood concentration compared with intramuscular CYT107. No cytokine storm and no formation of antibodies to CYT107 were observed. Intravenous CYT10...