IL-7 restores lymphocyte functions in septic patients.
Septic syndrome is the leading cause of mortality for critically ill patients worldwide. Patients develop lymphocyte dysfunctions associated with increased risk of death and nosocomial infections. In this study, we performed preclinical experiments testing the potential of recombinant human IL-7 (rhIL-7) as a lymphostimulating therapy in sepsis. Circulating IL-7 and soluble IL-7 receptor α-chain (soluble CD127) concentrations were measured in plasma, whereas cellular CD127 expression was evaluated on circulating CD4(+) and CD8(+) lymphocytes from septic shock patients and healthy volunteers. Lymphocyte proliferation, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction were measured ex vivo in response to T cell stimulation in the presence or not of rhIL-7. We show that IL-7 pathway (plasmatic IL-7 concentration and cellular and soluble CD127 expressions) is not overtly altered and remains activable in septic patients. Most importantly ex vivo treatment of patients' cells with rhIL-7 significantly improves lymphocyte functionality (CD4(+) and CD8(+) lymphocyte proliferations, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction after stimulation). To our knowledge, this constitutes the first report of rhIL-7 ability to restore normal lymphocyte functions in septic patients. These results support the rational for initiating a clinical trial testing rhIL-7 in septic shock.
Hospices Civils de Lyon, Laboratoire d'Immunologie Cellulaire, Hôpital E Herriot, 69003 Lyon, France.
Fabienne
F
Venet
Anne-Perrine
AP
Foray
Astrid
A
Villars-Méchin
Christophe
C
Malcus
Françoise
F
Poitevin-Later
Alain
A
Lepape
Guillaume
G
Monneret
D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology*
C508605:IL7 protein, human; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D007371:Interferon-gamma