Decreased frequencies of CD4+CD25+Foxp3+ cells and the potent CD103+ subset in peripheral lymph nodes correlate with autoimmune disease predisposition in some strains of mice.

The CD4(+)CD25(+)Foxp3(+) cells are essential for regulation of the immune response, and the integrin, CD103 (α(E)β(7)), identifies a potent subset of these cells. Defects in CD4(+)CD25(+)Foxp3(+) cells are thought to contribute to susceptibility to autoimmune disease in predisposed individuals. Studies evaluating the quality and quantity of CD4(+)CD25(+)Foxp3(+) regulatory cell populations in the context of autoimmune disease susceptibility have been inconclusive, and few if any, have analyzed the CD103 subset.

HE3286, an orally bioavailable synthetic analogue of an active DHEA metabolite suppresses spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse.

5-Androstene-3β,7β,17β-triol (AET) is a naturally occurring anti-inflammatory adrenal steroid that limits acute and chronic inflammation. HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol) is a synthetic derivative of AET with improved pharmaceutical properties and efficacy in some animal models of autoimmunity. Here, daily oral doses of HE3286 led to a suppression of spontaneous autoimmune diabetes in the non-obese diabetic mouse model of type 1 diabetes mellitus when administered either shortly before or after the first incidence of disease onset.

Short-term hyperglycemia in surgical patients and a study of related cellular mechanisms.

Objective: To examine cellular mechanisms by which short-term elevations of glucose or insulin impair leukocyte functions and to assess the occurrence of perioperative hyperglycemia in surgical patients.

Summary Background Data: A major factor in the contemporary management of the critically ill surgical patient is the progressively exact control of blood glucose. However, the separate role of insulin and underlying immunologic mechanisms are not well understood.

Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis.

Background: Hyperglycemia is an independent risk factor for increased mortality of critically ill surgical patients, but despite the recognized clinical benefits of early insulin treatment, there is a lack of understanding of the cellular and molecular mechanisms behind this phenomenon. We hypothesized that polymorphonuclear neutrophils, the first line of the innate immune defense system, suffer from altered apoptotic turnover when exposed to hyperglycemic conditions, ultimately decreasing the number of viable cells active at a site of infection.

Methods: Venous blood samples were drawn from 10 volunteers and incubated for 0.