PREVENTION OF THE CYTOTOXIC EFFECT OF IL-1 BY HUMAN LYSOZYME ON ISOLATED RAT ISLETS

Macrophages are present in the initial phase of the autoimmune process involved in the destruction of the endocrine pancreas in IDDM via the secretion of cytokines such as IL-1 beta. Macrophages also secrete ly sozyme. Besides its action on the bacterial cell wall, lysozyme has an important physiological and immunological role. Human lysozyme is an in-situ modulator of the inflammatory reactions. We investigate the pr otective role of human lysozyme in vitro against the cytotoxic effect of IL-1 beta or of IL-1 beta combined with IFN-gamma on isolated rat i slets. Precultured newborn rat islets were incubated with human or chi cken lysozyme (50.000 U/ml) over 3 days. Human IL-1 beta (100 U/ml) or IL-1 beta (5 U/ml) + INF-gamma (100 U/ml) was added for the last 2 da ys and tritiated thymidine for the last 24 hrs. In another set of expe riments, islets were exposed simultaneously to human lysozyme and IL-1 beta. Only pretreatment with human lysozyme abolished the lowering of the labelling index of the islet cell induced by IL-1 beta or by IL-1 beta and INF-gamma. Pycnotic nuclei were abundant in islets treated w ith IL-1 alone while they were not when islets were pretreated with hu man lysozyme. Chicken lysozyme had no protective effect in the same pr otocol. Human lysozyme was not protective when applied simultaneously with IL-1. Pretreatment of the islets by human lysozyme does not preve nt the reduction of the insulin secretion induced by IL-1 beta. Human and chicken lysozyme differ further in their action when tested on fib roblasts proliferation. Only human lysozyme stimulates the latter.-In conclusion, only human lysozyme seems to have a protective effect agai nst the cytotoxicity of IL-1 in combination or not with IFN-gamma on i slet cells in vitro. Moreover, to be protected, the islets have to be pretreated with lysozyme before the IL-1 application. Our in vitro res ults imply that natural aspecific immunity and its relation to the sec retory function of the macrophage might be crucial for the prevention of the initial assault responsible for the onset of the immune process leading to insulin dependent diabetes.