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

Transplantation
L BaiAnn M Simpson

Abstract

The cytokine tumour necrosis factor-alpha (TNF-alpha) is thought to be responsible for primary nonfunction of islets when transplanted. This, and two other cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) are also implicated in the autoimmune destruction of beta cells. It is unknown if the fetal pig beta cell, which is being transplanted as a treatment for type 1 diabetes, is affected by these cytokines. We compared the effects of the cytokines on the function and viability of adult and fetal pig beta cells. The cells were cultured for up to 3 days in the presence of 2000 pg/ml of human IL-1beta, 1000 U/ml of TNF-alpha, and 1000 U/ml of IFN-gamma, as well as 1000 U/ml of porcine IFN-gamma. 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. TNF-alpha and the combination of the three human cytokines caused a transient increase in cumulative insulin levels. TNF-alpha alone enhanced insulin content on day 3. There was no effect of these human cytokines on mitochondrial function and viability. In contrast, porcine IFN-gamma inhibited fetal ...Continue Reading

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Citations

Jun 15, 2007·Transplantation·Jayne L FosterBernard E Tuch
Aug 12, 2004·Xenotransplantation·Lijun BaiBernard E Tuch
May 21, 2015·Journal of Zhejiang University. Science. B·Hai-tao ZhuBo Wang
Mar 26, 2014·Tissue Barriers·Raphael LabensAnthony T Blikslager
May 21, 2019·Clinical Medicine Insights. Endocrinology and Diabetes·Varun PathakReinhold J Medina

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