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


OBJECTIVE
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.


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.
Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97216, USA.
Stefanie N
SN
Linch
Erin T
ET
Danielson
Ann M
AM
Kelly
Raina A
RA
Tamakawa
James J
JJ
Lee
Jeffrey A
JA
Gold
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D016019:Survival Analysis
D016207:Cytokines; D015848:Interleukin-5; D015850:Interleukin-6; D016753:Interleukin-10