title: Interleukin 4 Deficiency Reverses Development of Secondary Pseudomonas aeruginosa Pneumonia During Sepsis-Associated Immunosuppression.
abstract: BACKGROUND
  Interleukin 4 (IL-4) is an important cytokine that may modulate development of secondary bacterial pneumonia during sepsis-induced immunosuppression.
  
  
  METHODS
  We established an experimental model of cecal ligation and puncture (CLP)-induced sublethal polymicrobial sepsis followed by secondary Pseudomonas aeruginosa pulmonary infection,
  
  
  RESULTS
  IL-4-deficient mice that underwent CLP were resistant to secondary pulmonary P. aeruginosa infection. As compared to wild-type mice, IL-4 knockout (KO) mice displayed improved survival and better bacterial clearance. Furthermore, IL-4 KO mice exhibited enhanced lung inflammation, neutrophil recruitment to airspaces, and elevated pulmonary cytokine production, with significantly increased tumor necrosis factor α (TNF-α) production. Neutralization of TNF-α could reverse the enhanced protection against secondary P. aeruginosa pneumonia in septic IL-4 KO mice, indicating that the resistance of septic IL-4 KO mice to secondary bacterial pneumonia was partially mediated by TNF-α. In addition, IL-4 priming displayed marked impairment of the ability of alveolar macrophages to phagocytose and kill P. aeruginosa in vitro, and this defect was associated with decreased activation of Akt, JNK, p38MAPK, and ERK intracellular signaling pathways by IL-4. Finally, neutralization of IL-4 in septic mice could improve survival and clearance of bacteria from the lungs of septic mice infected with P. aeruginosa.
  
  
  CONCLUSIONS
  Our findings provide new insight for immunopathologic mechanisms of sepsis-induced secondary bacterial pneumonia.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Song
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Dagen
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University.
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000172:deficiency*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D018805:Sepsis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4
keywords: IL-4; immunopathology; immunosuppression; pneumonia; sepsis