Role of endogenous IL-6 in the neonatal expansion and functionality of Wistar rat pancreatic alpha cells.

Aims/hypothesis: Plasma glucagon concentrations rise sharply during the early postnatal period. This condition is associated with increased alpha cell mass. However, the trophic factors that regulate alpha cell turnover during the perinatal period have not been studied. Macrophage infiltrations are present in the neonatal pancreas, and this cell type releases cytokines such as IL-6. Alpha cells have been identified as a primary target of IL-6 actions. We therefore investigated the physiological relevance of IL-6 to neonatal pancreatic alpha cell maturation.

Methods: Histochemical analyses were performed to quantify alpha cell mass, replication and apoptosis. Pancreatic Il6 expression was determined by quantitative RT-PCR. The biological effect of IL-6 was tested in two in vivo rat models of IL-6 blockade and chronic undernutrition.

Results: Alpha cell mass increased sharply shortly after birth but decreased significantly after weaning. Pancreatic alpha cell proliferation was as high as 2.5% at the beginning of suckling but diminished with time to 1.2% in adulthood. Similarly, alpha cell neoformation was remarkably high on postnatal day (PN) 4, whereas alpha cell apoptosis was low throughout the neonatal period. Moreover, Il6 mRNA exhibited developmental upregulation in the pancreas of suckling rats, with the highest expression on PN2. Neutralisation of IL-6 reduced alpha cell mass expansion and glucagon production. IL-6 staining was detected within the islets, mainly in the alpha cells. Finally, undernourished neonates showed altered alpha cell number and function and delayed appearance of IL-6 in the pancreas.

Conclusions/interpretation: These data point to a potential role for local IL-6 in the regulation of alpha cell growth and function during suckling.