The central response to ovarian carcinoma simulates the response to sepsis

Linda F. Carson, Sabita Roy, Kelly Cain, Richard Charboneau, Stanley Deturris, S. Ramakrishin, Roderick A. Barke

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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. Materials and 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/EBPα 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 cfos mRNA increased >8-fold (P < 0.001); and (4) lung C/EBPα 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.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalJournal of Surgical Research
Volume75
Issue number2
DOIs
StatePublished - Mar 1998
Externally publishedYes

Keywords

  • IL-1
  • IL-6
  • Ovarian carcinoma
  • c-fos

ASJC Scopus subject areas

  • Surgery

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