title: STAT5 phosphorylation in T cell subsets from septic patients in response to recombinant human interleukin-7: a pilot study.
abstract: Septic shock is characterized by lymphocyte alterations associated with increased risk of nosocomial infections and mortality. IL-7, a cytokine required for T cell survival, is thought as a novel therapy for septic patients with severe lymphopenia. We assessed CD4(+) lymphocyte responsiveness to rhIL-7 in septic shock patients ex vivo. Thirteen septic shock patients and 10 controls were included. The MFI of pSTAT5, a key signaling molecule for IL-7, was measured by flow cytometry in CD4(+)FOXP3- (Teffs) and CD4(+)FOXP3(+) (Tregs) lymphocytes after whole-blood incubation with increasing doses of rhIL-7. The basal level of pSTAT5 in nonstimulated T cells was higher in patients. However, the maximal activation level in response to the highest doses of rhIL-7 was similar in both groups. Importantly, low doses of rhIL-7 preferentially activated Teff versus Treg in patients and nonsurvivors tended to present with decreased pSTAT5 expression. This pilot study is the first to highlight, in septic patients, the interest of pSTAT5 measurement in whole blood for the monitoring of rhIL-7 therapy. Such a method could represent an innovative, biologic tool for monitoring leukocyte pharmacological responses to biotherapies in daily clinical practice in other clinical contexts.
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Demaret
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dupont
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Friggeri
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rimmelé
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Morel
authors.affiliation: *Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France guillaume.monneret@chu-lyon.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
mesh_terms: D000368:Aged; D015415:Biomarkers; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D016867:Immunocompromised Host; D066298:In Vitro Techniques; D015851:Interleukin-7 / Q000494:pharmacology*; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology / Q000401:mortality; D010766:Phosphorylation; D010865:Pilot Projects; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508605:IL7 protein, human; D015851:Interleukin-7; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D014662:Vasoconstrictor Agents
keywords: immunosuppression; sepsis; septic shock