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