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Abstract
Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1β (IL-1β) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats. In contrast, high dose injections induced an earlier than normal onset. In this study we tested whether the effects of daily human recombinant IL-1β injections on leukocyte subsets were associated with its modulation of IDDM onset in BB rats. Prior to the onset of IDDM in DP BB rats, high dose IL-1 β induced leukocytosis (P < 0.05), neutrophilia (P<0.01), and monocytosis (P < 0.001). At the onset of IDDM, lymphocyte (P < 0.01) and neutrophil (P<0.001) numbers were increased in high dose treated DP rats but not in rats given saline or low dose IL-1β. In 60-day-old diabetes-resistant (DR) BB rats, neurophilia was induced by both low (P<0.05) and high (P<0.001) dose IL-1 β without the development of IDDM. At 130 days of age, when the rats were killed, it was discovered that 14/22 (64%) IL-1β injected DR rats developed neutralizing IL-1β antibodies. Significantly lower neutrophil numbers were observed in high dose DR rats which developed IL-1β antibodies compared with those which did not (P=0.032). Thus, neutrophilia was dissociated from high IL-1β acceleration of IDDM onset. These results suggest that acceleration of diabetogenesis in DP rats by IL-1β is associated with increased prediabetic levels of monocytes at 60 days of age and of lymphocytes at onset of IDDM.