The destructive action of IL-1 alpha and IL-1 beta in IDDM is a multistageprocess: evidence and confirmation by apoptotic studies, induction of intermediates and electron microscopy

USING the rat beta-cell RIN-5AH insulinoma line as a means for studying ins ulin-dependent diabetes mellitus (IDDM), it is shown that interleukin-1 (IL -1) induces beta-cell damage initiated by early apoptotic signals. This act ion is demonstrated by DNA fragmentation, as assessed by specific BrdU labe ling, surface expression of Fas and nitric oxide (NO) production. In additi on, the interplay between NO and Fas is shown, while scanning electron micr oscopy (SEM) confirms apoptosis by revealing the degree and type of cellula r damage which, in the case of IL-1 alpha, can be reversed by an inhibitor to NO synthesis. Apoptosis is also reconfirmed by transmission electron mic roscopy (TEM) by observing condensed nuclear chromatin after IL-1 exposure. Thus, treatment of insulinoma cells with IL-1 alpha and IL-1 beta seems to initiate a number of signals, including PKC activation as published previo usly, that ultimately lead to beta-cell destruction. Each IL-1 isoform, how ever, definitely follows a different pathway of action.