Search

Interleukin 1β has been proposed to play an essential role in the pathogenesis of IDDM by direct interaction with the pancreatic beta-cell. Glucocorticoids are widely used as immunosuppressive agents and have been suggested to interfere both with the production and action of interleukin 1. The aim of the present study was to evaluate the interaction between cortisol and interleukin-1 on the pancreatic beta-cell function in vitro. Newborn rat islets were precultured for seven days before they were exposed to interleukin 1 with or without addition of cortisol. The release of insulin to the culture medium was followed and the insulin content and biosynthesis were measured after one week in culture. Cortisol, 10−6mol/l, resulted in a 50% lower rate of release during the culture period and a similar reduction in storage and biosynthesis of insulin in the islets at the end of the culture period. In the control islets interleukin 1, 0.5 μg/l, resulted in an early increase in insulin release followed by a marked reduction. In the cortisol-treated islets interleukin 1 increased the release up to 72 h followed by a moderate decrease. In the control islets, interleukin 1 reduced the insulin content to about 50%, whereas in the cortisol-treated islets interleukin 1 resulted in an even greater reduction, to about 30%. This additional effect of cortisol seems not to be due to an augmented cytotoxic effect of interleukin 1 as indicated by the DNA content of the islets and the viability of the cells. In conclusion, cortisol treatment augmented both the early stimulatory and the late inhibitory effects of interleukin 1 on insulin release and biosynthesis in isolated pancreatic islets in culture.

The intestine is the primary reservoir of Candida albicans that can cause systemic infections in immunocompromised patients. In this reservoir, the fungus exists as a harmless commensal. However, antibiotic treatment can disturb the bacterial microbiota, facilitating fungal overgrowth and favoring pathogenicity. The current in vitro gut models that are used to study the pathogenesis of C. albicans investigate the state in which C. albicans behaves as a pathogen rather than as a commensal. We present a novel in vitro gut model in which the fungal pathogenicity is reduced to a minimum by increasing the biological complexity. In this model, enterocytes represent the epithelial barrier and goblet cells limit C. albicans adhesion and invasion. Significant protection against C. albicans-induced necrotic damage was achieved by the introduction of a microbiota of antagonistic lactobacilli. We demonstrated a time-, dose- and species-dependent protective effect against C. albicans-induced cytotoxicity. This required bacterial growth, which relied on the presence of host cells, but was not dependent on the competition for adhesion sites. Lactobacillus rhamnosus reduced hyphal elongation, a key virulence attribute. Furthermore, bacterial-driven shedding of hyphae from the epithelial surface, associated with apoptotic epithelial cells, was identified as a main and novel mechanism of damage protection. However, host cell apoptosis was not the driving mechanism behind shedding. Collectively, we established an in vitro gut model that can be used to experimentally dissect commensal-like interactions of C. albicans with a bacterial microbiota and the host epithelial barrier. We also discovered fungal shedding as a novel mechanism by which bacteria contribute to the protection of epithelial surfaces. This article has an associated First Person interview with the joint first authors of the paper.