Interleukin-6 induces thermotolerance in cultured Caco-2 cells independent of the heat shock response

Dan D. Hershko, Bruce W. Robb, Guang Ju Luo, James H. Paxton, Per Olof Hasselgren

Research output: Contribution to journalArticle

14 Scopus citations


In recent studies, induction of the heat shock response increased IL-6 production in gut mucosa in vivo and in cultured Caco-2 cells in vitro. The heat shock response is associated with increased survival of cells exposed to otherwise lethal hyperthermia, so called thermotolerance, but the role of IL-6 in the induction of thermotolerance is not known. We tested the hypothesis that treatment of cultured Caco-2 cells with IL-6 results in the development of thermotolerance. Cells were treated with human recombinant IL-6 for 1 h followed by 3 h recovery in cytokine-free medium whereafter cells were exposed to heat stress (48°C for 2 h). In untreated cells, the heat stress resulted in an approximately 80% cell death. In cells treated with IL-6, cell viability after heat stress was significantly improved and was doubled at an IL-6 concentration of 20 ng/ml. Treatment of the cells with other cytokines (IL-4, IL-10, IL-1β, or TNFα) did not induce thermotolerance, suggesting that the effect of IL-6 may be specific for this cytokine. The induction of thermotolerance by IL-6 was blocked by an IL-6 receptor antibody, suggesting that the development of thermotolerance was receptor-mediated. Treatment of cells with IL-6 did not induce an heat shock response as suggested by unaltered heat shock protein 70 and 90 levels and unaffected heat shock factor DNA binding activity. In addition, the IL-6-induced thermotolerance was not inhibited by quercetin. The present study provides the first evidence of IL-6-induced thermotolerance and suggests that this effect of IL-6 is independent of the heat shock response.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
Issue number1
StatePublished - Jan 7 2003
Externally publishedYes


  • Cell protection
  • Cytokines
  • Enterocytes
  • Mucosa
  • Proteasome inhibition

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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