title: The central response to ovarian carcinoma simulates the response to sepsis.
abstract: BACKGROUND
  Animal models of stress and sepsis demonstrate increased hypophyseal gene expression of the transcription factor c-fos and the cytokines interleukin-1 and interleukin-6. Chronic central nervous system exposure to interleukin-1 results in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia. We test the hypothesis that the host response to ovarian carcinoma recapitulates the host response to sepsis regarding the elaboration of the transcription factors and cytokines in the central nervous system, liver, and lung.
  
  
  METHODS
  Nude mice were seeded intraperitoneally with either ovarian carcinoma (MA-148) or vehicle. The animal subjects were observed for 5 weeks and sacrificed for brain, pituitary, lung, and liver mRNA. We studied the mRNA accumulation of the transcription factors c-fos, c-jun, and C/EBP alpha and the cytokines interleukin-1 and interleukin-6 using reverse-transcriptase polymerase chain reaction.
  
  
  RESULTS
  Compared with the control, ovarian carcinoma in the mouse model resulted in the following: (1) Pituitary c-fos and c-jun mRNA increased 3-fold (P = 0.012) and 6-fold (P < 0.001), respectively; (2) pituitary IL-1 and IL-6 mRNA increased 4-fold (P < 0.001) and 8-fold (P = 0.037), respectively; (3) liver c-fos mRNA increased > 8-fold (P < 0.001); and (4) lung C/EBP alpha mRNA decreased greater than 10-fold (P < 0.001).
  
  
  CONCLUSIONS
  We conclude that the host response to ovarian carcinoma in this animal model recapitulates many aspects of the host response to bacterial sepsis especially concerning pituitary gene expression. These data suggest that, as in sepsis, a hypothalamic-hypophyseal-mediated cytokine response in ovarian carcinoma may result in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia.
authors.affiliation: Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Carson
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: K
authors.initials: K
authors.lastname: Cain
authors.forename: R
authors.initials: R
authors.lastname: Charboneau
authors.forename: S
authors.initials: S
authors.lastname: DeTurris
authors.forename: S
authors.initials: S
authors.lastname: Ramakrishin
authors.forename: R A
authors.initials: RA
authors.lastname: Barke
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002277:Carcinoma / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D007239:Infections / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010902:Pituitary Gland / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger