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Interleukin 5 is protective during sepsis in an eosinophil-independent manner.

Abstract：

RATIONALE:The immune response in sepsis is characterized by overt immune dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests a potentially protective role for interleukin 5 (IL-5) in sepsis; however, the loss of eosinophils in this disease presents a paradox. OBJECTIVES:To assess the protective and eosinophil-independent effects of IL-5 in sepsis. METHODS:We assessed the effects of IL-5 administration on survival, bacterial burden, and cytokine production after polymicrobial sepsis. In addition, we examined the effects on macrophage phagocytosis and survival using fluorescence microscopy and flow cytometry. MEASUREMENTS AND MAIN RESULTS:Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10 production, and bacterial burden during sepsis. Therapeutic administration of IL-5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils resulted in decreased mortality from sepsis and increased circulating neutrophils and monocytes, suggesting their importance in the protective effects of IL-5. Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis, and survival of macrophages. Importantly, macrophage depletion before the onset of sepsis eliminated IL-5-mediated protection. The protective effects of IL-5 were confirmed in humans, where IL-5 levels were elevated in patients with sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5 receptor. CONCLUSIONS:Taken together, these data support a novel role for IL-5 on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a viable therapy for sepsis.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Linch SN,Danielson ET,Kelly AM,Tamakawa RA,Lee JJ,Gold JA

doi

10.1164/rccm.201201-0134OC

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

246-54

issue

eissn

1073-449X

issn

1535-4970

pii

rccm.201201-0134OC

journal_volume

186

pub_type

杂志文章

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Interleukin 5 is protective during sepsis in an eosinophil-independent manner.