Islet cytotoxicity of interleukin 1. Influence of culture conditions and islet donor characteristics

Abstract

We recently demonstrated that the macrophage product interleukin 1 (IL-1) is cytotoxic to isolated pancreatic islets and hypothesized that IL-1 is responsible for beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). We studied whether the variation in IDDM preponderance with age, sex, and genetic background in vivo is reflected in different susceptibility to IL-1 toxicity of islets in vitro. In addition, we studied the effect of preculture conditions that support endocrine islet cell function and decrease nonendocrine passenger-cell survival on the susceptibility of beta-cells to IL-1 because it is unknown whether IL-1 acts directly on beta-cells or via passenger cells. No differences in susceptibility to various doses of IL-1-containing mononuclear cell supernatants were found between islets isolated from newborn or adult rats, male or female rats, or rats of four inbred strains, indicating that age, sex, and genetic background do not influence the susceptibility of the beta-cell to IL-1. Preculture of islets for 1-7 days in normal atmosphere and preculture of islet clusters in 95% O2 to delete passenger cells did not affect IL-1-mediated cytotoxicity, suggesting that IL-1 acts directly on beta-cells. Increasing the glucose concentration (22 mM) in the culture medium, which is known to protect beta-cells against alloxan toxicity, reduced IL-1 toxicity. Five or 25% normal human serum as well as 5% normal rat serum, but not equivalent concentrations of human serum albumin, inhibited IL-1 toxicity, indicating the presence of IL-1 inhibitors, IL-1 antagonists, or beta-cell-protecting factors in normal serum.(ABSTRACT TRUNCATED AT 250 WORDS)