{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:17:03Z","timestamp":1789863423624,"version":"4.0.1"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014677","name":"George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures","doi-asserted-by":"publisher","award":["10126\/17.12.2020"],"award-info":[{"award-number":["10126\/17.12.2020"]}],"id":[{"id":"10.13039\/501100014677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Sepsis triggers a complex immune response, disrupting the balance between pro- and anti-inflammatory signals and causing widespread immune cell apoptosis. Interleukin 7 (IL-7) is emerging as one of the most promising immunoadjuvants to boost host immunity during the immunosuppressive phase of the disorder. This study aimed to investigate the dynamics of endogenous plasma levels of IL-7 during sepsis and septic shock, correlating its levels with lymphopenia and various lymphocyte subtypes, including CD4+ and CD8+ T cells, B cells, and natural killer T cells (NKT), in both survivors and non-survivors. Materials and Methods: This prospective observational study included 87 critically ill patients. We categorized the patients into four subgroups based on their diagnosis (sepsis or septic shock) and survival status (survivors and non-survivors). The parameters were monitored on day 1 (when sepsis was diagnosed according to the Sepsis-3 Consensus) and again on day 5. Eighty-two healthy volunteers were included as a control group to establish the cut-off values for IL-7. Results: Statistical analysis revealed a significant difference in median values between days 1 and 5 for lymphocytes (p = 0.01) and NKT cells (p = 0.01), observed only in sepsis survivors. In the group of sepsis survivors, we observed a negative correlation between IL-7 levels and NKT cells but only on day 1. Additionally, we identified negative correlations between Th cells (CD4+) and Tc cells (CD8+) on both day 1 and day 5. In the group of sepsis non-survivors, we observed a positive correlation between IL-7 and B cells (CD19+) but only on day 1. We also identified a negative correlation between Th cells (CD4+) and Tc cells (CD8+) on day 1. In the group of septic shock survivors, we did not observe any correlation between IL-7 levels and other parameters studied on day 1 or day 5. We identified a negative correlation between Th cells (CD4+) and Tc cells (CD8+) on both day 1 and day 5, a negative correlation between Th cells (CD4+) and NKT cells on both day 1 and day 5, and a positive correlation between Th cells (CD4+) and B cells (CD19+) on day 1. In the group of septic shock non-survivors, we did not observe any correlation between IL-7 and other parameters studied. Conclusions: Determining the IL-7 plasmatic value every five days did not demonstrate the necessary sensitivity and specificity as a biomarker to accurately assess each patient\u2019s immune balance. Endogenous IL-7 levels appear inadequate to overcome the immunosuppressive environment induced by sepsis.<\/jats:p>","DOI":"10.3390\/medicina61020258","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endogenous IL-7 Variation in Relation to Lymphocyte Subtypes in Septic Patients"],"prefix":"10.3390","volume":"61","author":[{"given":"Raluca-\u0218tefania","family":"Fodor","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-266X","authenticated-orcid":false,"given":"Alice","family":"Dr\u0103goescu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Coman","sequence":"additional","affiliation":[{"name":"Department of Simulation Applied in Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9798-1594","authenticated-orcid":false,"given":"Adina","family":"Hu\u021banu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Centre for Advanced Medical and Pharmaceutical Research, Immunology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9473-0287","authenticated-orcid":false,"given":"Anca","family":"Bac\u00e2rea","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca-Liana","family":"Grigorescu","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1056\/NEJM199606273342603","article-title":"Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group","volume":"334","author":"Fisher","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The immune system\u2019s role in sepsis progression, resolution, and long-term outcome","volume":"274","author":"Delano","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, X., Xu, Z., Pang, X., Huang, Y., Yang, B., Yang, Y., Chen, K., Liu, X., Mao, P., and Li, Y. (2017). Interleukin-10\/lymphocyte ratio predicts mortality in severe septic patients. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179050"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1080\/00365540310015692","article-title":"Role of apoptotic cell death in sepsis","volume":"35","author":"Hotchkiss","year":"2003","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1189\/jlb.0105017","article-title":"Leukocyte apoptosis and its significance in sepsis and shock","volume":"78","author":"Wesche","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e98960","DOI":"10.1172\/jci.insight.98960","article-title":"Interleukin-7 restores lymphocytes in septic shock: The IRIS-7 randomized clinical trial","volume":"3","author":"Francois","year":"2018","journal-title":"JCI Insight"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1615\/CritRevImmunol.2018027460","article-title":"IL-7 and Its Beneficial Role in Sepsis-Induced T Lymphocyte Dysfunction","volume":"38","author":"Monneret","year":"2018","journal-title":"Crit. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1189\/jlb.4A1215-581R","article-title":"Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia","volume":"101","author":"Shindo","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.smim.2012.04.011","article-title":"Interleukin 7, maestro of the immune system","volume":"24","author":"Sprent","year":"2012","journal-title":"Semin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1182\/blood-2012-06-437236","article-title":"Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation","volume":"120","author":"Perales","year":"2012","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/cid\/cis383","article-title":"Effects of recombinant human interleukin 7 on T-Cell recovery and thymic output in HIV-Infected patients receiving antiretroviral therapy: Results of a Phase I\/IIA randomized, Placebo-Controlled, Multicenter study","volume":"55","author":"Levy","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1182\/blood-2008-10-186601","article-title":"IL-7 administration drives T cell\u2013cycle entry and expansion in HIV-1 infection","volume":"113","author":"Sereti","year":"2009","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1182\/blood-2015-05-645077","article-title":"Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia","volume":"127","author":"Sheikh","year":"2015","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/01.cji.0000210386.55951.c2","article-title":"IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-Regulatory cells","volume":"29","author":"Rosenberg","year":"2006","journal-title":"J. Immunother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"B\u00e9nard, A., Hansen, F.J., Uhle, F., Kl\u00f6sch, B., Czubayko, F., Mittelst\u00e4dt, A., Jacobsen, A., David, P., Podolska, M.J., and Anthuber, A. (2023). Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1140630"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/infdis\/jis383","article-title":"Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis","volume":"206","author":"Unsinger","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.4049\/jimmunol.0903151","article-title":"IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis","volume":"184","author":"Unsinger","year":"2010","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156277","DOI":"10.1016\/j.cyto.2023.156277","article-title":"Interleukin-7 and interleukin-15 as prognostic biomarkers in sepsis and septic shock: Correlation with inflammatory markers and mortality","volume":"169","author":"Janc","year":"2023","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, D., Tang, T.X., Deng, H., Yang, X.P., and Tang, Z.H. (2021). Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.747324"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ampuero, S., Bahamonde, G., Tempio, F., Garmendia, M.L., Ruiz, M., Pizarro, R., Rossi, P., Huenchur, L., Lizama, L., and L\u00f3pez, M. (2022). IL-7\/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): A cross-sectional study. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-13063-x"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/ni1395","article-title":"A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127","volume":"7","author":"Vosshenrich","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nedeva, C. (2021). Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis. Biomolecules, 11.","DOI":"10.3390\/biom11071011"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/SHK.0000000000000495","article-title":"Immune cell phenotype and function in sepsis","volume":"45","author":"Payen","year":"2016","journal-title":"Shock"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1365-2567.2004.02089.x","article-title":"Interleukin-7 signalling is sufficient to phenotypically and functionally prime human CD4 naive T cells","volume":"114","author":"Managlia","year":"2005","journal-title":"Immunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/00024382-200212000-00001","article-title":"Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome","volume":"18","author":"Pangault","year":"2002","journal-title":"Shock"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:59Z","timestamp":1760027159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,2]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["medicina61020258"],"URL":"https:\/\/doi.org\/10.3390\/medicina61020258","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,2]]}}}