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

Stefanie N. Linch, Erin T. Danielson, Ann M. Kelly, Raina A. Tamakawa, James J. Lee, Jeffrey A. Gold

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)246-254
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume186
Issue number3
DOIs
StatePublished - Aug 1 2012

Fingerprint

Interleukin-5
Eosinophils
Sepsis
Interleukin-5 Receptors
Monocytes
Neutrophils
Macrophages
Phagocytosis
Mortality
Cytokines
Survival
Neutrophil Infiltration
Therapeutics
Fluorescence Microscopy
Interleukin-10
Immunization
Interleukin-6
Flow Cytometry

Keywords

  • Immunotherapy
  • Innate immunity
  • Macrophages
  • Neutrophils

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Linch, S. N., Danielson, E. T., Kelly, A. M., Tamakawa, R. A., Lee, J. J., & Gold, J. A. (2012). Interleukin 5 is protective during sepsis in an eosinophil-independent manner. American Journal of Respiratory and Critical Care Medicine, 186(3), 246-254. https://doi.org/10.1164/rccm.201201-0134OC

Interleukin 5 is protective during sepsis in an eosinophil-independent manner. / Linch, Stefanie N.; Danielson, Erin T.; Kelly, Ann M.; Tamakawa, Raina A.; Lee, James J.; Gold, Jeffrey A.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 186, No. 3, 01.08.2012, p. 246-254.

Research output: Contribution to journalArticle

Linch, Stefanie N. ; Danielson, Erin T. ; Kelly, Ann M. ; Tamakawa, Raina A. ; Lee, James J. ; Gold, Jeffrey A. / Interleukin 5 is protective during sepsis in an eosinophil-independent manner. In: American Journal of Respiratory and Critical Care Medicine. 2012 ; Vol. 186, No. 3. pp. 246-254.
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