Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis.

Abstract

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.

• Authors: Jacqueline Unsinger, Carey-Ann D Burnham, Jacquelyn McDonough, Michel Morre, Priya S Prakash, Charles C Caldwell, W Michael Dunne Jr, Richard S Hotchkiss
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 206 Issue 4 Pg. 606-16 (Aug 15 2012) ISSN: 1537-6613 [Electronic] United States
• PMID: 22693226 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Immunologic Factors
• Interleukin-7

Topics

• Animals
• Candida albicans (pathogenicity)
• Candidemia (drug therapy, immunology, microbiology, mortality)
• Disease Models, Animal
• Immunologic Factors (administration & dosage, immunology)
• Interleukin-7 (administration & dosage, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Sepsis (drug therapy, immunology, microbiology, mortality)
• Survival Analysis
• Treatment Outcome