title: Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines.
abstract: 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.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Sezione Metabolismo, Università di Pisa, Via Paradisa 2, 56100 Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marselli
authors.forename: F
authors.initials: F
authors.lastname: Dotta
authors.forename: S
authors.initials: S
authors.lastname: Piro
authors.forename: C
authors.initials: C
authors.lastname: Santangelo
authors.forename: M
authors.initials: M
authors.lastname: Masini
authors.forename: R
authors.initials: R
authors.lastname: Lupi
authors.forename: M
authors.initials: M
authors.lastname: Realacci
authors.forename: S
authors.initials: S
authors.lastname: del Guerra
authors.forename: F
authors.initials: F
authors.lastname: Mosca
authors.forename: U
authors.initials: U
authors.lastname: Boggi
authors.forename: F
authors.initials: F
authors.lastname: Purrello
authors.forename: R
authors.initials: R
authors.lastname: Navalesi
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D005947:Glucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007371:Interferon-gamma / Q000633:toxicity; D007375:Interleukin-1 / Q000633:toxicity; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018418:Th2 Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D007328:Insulin; D007375:Interleukin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D005947:Glucose