Fetal pig β cells are resistant to the toxic effects of human cytokines

Lijun Bai, Bernard E. Tuch, Bernhard Hering, Ann M. Simpson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background. The cytokine tumour necrosis factor-α (TNF-α) is thought to be responsible for primary non-function of islets when transplanted. This, and two other cytokines, interleukin-1β (IL-1β) and interferon -γ (IFN-γ) are also implicated in the autoimmune destruction of β cells. It is unknown if the fetal pig β cell, which is being transplanted as a treatment for type 1 diabetes, is affected by these cytokines. Methods. We compared the effects of the cytokines on the function and viability of adult and fetal pig β cells. The cells were cultured for up to 3 days in the presence of 2000 pg/ml of human IL-1β, 1000 U/ml of TNF-α, and 1000 U/ml of IFN-γ, as well as 1000 U/ml of porcine IFN-γ Cumulative insulin levels, insulin content, metabolic activity, and viability of these cells were examined. Additionally, nitric oxide production and the activity of antioxidant enzymes in these cells were also determined. Results. TNF-α and the combination of the three human cytokines caused a transient increase in cumulative insulin levels. TNF-α alone enhanced insulin content on day 3. There was no effect of these human cytokines on mitochondrial function and viability. In contrast, porcine IFN-γ inhibited fetal pig β cell function and also caused their death. Adult pig islets are sensitive to the toxic effects of human TNF-α, IL-1β, the combination of the three cytokines, and porcine IFN-γ. The activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase were significantly higher in fetal pig β cells than in adult islets, implying that this may be the reason for the lack of adverse effects of the cytokines on the fetal β cell. Conclusion. Fetal pig β cells are resistant to the toxic effect of the human cytokines, TNF-α and IL-1β, in vitro. This resistance suggests that fetal, but not adult β cells, when transplanted into humans with type 1 diabetes may be protected from primary nonfunction and will be partially protected from autoimmune destruction.

Original languageEnglish (US)
Pages (from-to)714-722
Number of pages9
Issue number5
StatePublished - Mar 15 2002


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