title: Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.
abstract: BACKGROUND
  Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.
  
  
  METHODS
  C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.
  
  
  RESULTS
  Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.
  
  
  CONCLUSIONS
  Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used.
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Lyons
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Fay
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Margoles
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Burd
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Alton B
authors.initials: AB
authors.lastname: Farris
authors.affiliation: Department of Surgery and Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.affiliation: Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Coopersmith
mesh_terms: D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3; D009195:Peroxidase