Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis.
BACKGROUND
Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-hit model of fungal sepsis.


METHODS
Mice underwent cecal ligation and puncture to induce peritonitis. Four days later, surviving mice had intravenous injection with Candida albicans. Following Candida infection, mice were treated with IL-7 or saline control. The effect of IL-7 on host immunity and survival was recorded.


RESULTS
IL-7 ameliorated the loss of immune effector cells and increased lymphocyte functions, including activation, proliferation, expression of adhesion molecules, and interferon-γ production. These beneficial effects of IL-7 were associated with an increase in global immunity as reflected by an enhanced delayed type hypersensitivity response and a 1.7-fold improvement in survival.


CONCLUSIONS
The present findings showing that IL-7 improves survival in fungal sepsis, together with its previously reported efficacy in bacterial and viral infectious models, further supports its use as a novel immunotherapeutic in sepsis.
Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Jacqueline
J
Unsinger
Carey-Ann D
CA
Burnham
Jacquelyn
J
McDonough
Michel
M
Morre
Priya S
PS
Prakash
Charles C
CC
Caldwell
W Michael
WM
Dunne
Richard S
RS
Hotchkiss
D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity; D058387:Candidemia / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D016019:Survival Analysis; D016896:Treatment Outcome
D007155:Immunologic Factors; D015851:Interleukin-7