TY - JOUR
T1 - Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis
AU - Unsinger, Jacqueline
AU - Burnham, Carey Ann D.
AU - McDonough, Jacquelyn
AU - Morre, Michel
AU - Prakash, Priya S.
AU - Caldwell, Charles C.
AU - Dunne, W. Michael
AU - Hotchkiss, Richard S.
N1 - Funding Information:
Potential conflicts of interest. M. M. is CEO of Cytheris, which holds the patent on use of IL-7 in sepsis and other diseases, including cancer and viral infections. R. S. H. has research funding from Pfizer for the study of anti-CTLA4 in vitro in sepsis. All other authors report no potential conflicts.
Funding Information:
Financial support. This work was supported by funding from the National Institute of General Medical Sciences (NIGMS; GM 44118 and GM 55194).
PY - 2012/8/15
Y1 - 2012/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866936380&partnerID=8YFLogxK
U2 - 10.1093/infdis/jis383
DO - 10.1093/infdis/jis383
M3 - Article
C2 - 22693226
AN - SCOPUS:84866936380
SN - 0022-1899
VL - 206
SP - 606
EP - 616
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -