Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines

J Clin Endocrinol Metab. 2001 Oct;86(10):4974-8. doi: 10.1210/jcem.86.10.7938.


Studies in rodents have suggested that Th2 and Th3 cytokines can be effective in reducing proinflammatory and Th1 cytokine-induced islet damage. Whether this is the case with human islets and might be due to a direct action of Th2 and Th3 cytokines is not known. In the present study, we evaluated whether Th2 (500 U/ml IL-4 plus 100 U/ml IL-10) or Th3 (5 ng/ml TGF-1beta) cytokines may prevent the derangements induced on isolated human islets by prolonged (12 or 72 h) exposure to combined proinflammatory (50 U/ml IL-1beta, 1000 U/ml TNF alpha) and Th1 (1000 U/ml interferon gamma) cytokines. Compared with control islets, cells preincubated for 12 or 72 h with proinflammatory and Th1 cytokines showed a significant decrease of glucose-stimulated insulin secretion and a significant increase of nitrites production. The addition of IL-4 plus IL-10 or TGF-1beta in the medium prevented these cytostatic effects in the 12-h incubation experiments, but not after the 72-h exposure period. IL-1beta, interferon gamma, and TNF alpha caused no major change in either islet cell survival or Bcl-2 and Bax mRNA expression after a 12-h incubation; however, a marked increase in the amount of dead cells, with a major decrease of Bcl-2 mRNA expression, was observed after 72 h. The presence of Th2, but not of Th3, cytokines significantly reduced beta-cell death, without any major effect on Bcl-2 and Bax mRNA expression. These results suggest that Th2 and (at lower extent) Th3 cytokines may have a partial, direct protective effect on isolated human islets exposed to the cytostatic and cytotoxic action of proinflammatory and Th1 cytokines.

MeSH terms

  • Glucose / pharmacology
  • Humans
  • In Vitro Techniques
  • Insulin / metabolism
  • Insulin Secretion
  • Interferon-gamma / toxicity
  • Interleukin-1 / toxicity
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology
  • Islets of Langerhans / ultrastructure
  • Nitric Oxide / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Th2 Cells / physiology*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / toxicity


  • Insulin
  • Interleukin-1
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Nitric Oxide
  • Interferon-gamma
  • Glucose