Cytokines Cause Functional and Structural Damage to Isolated Islets of Langerhans

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Abstract
Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin-dependent diabetes mellitus, isolated human or rat islets of Langerhans were incubated for 7 days with cytokine-rich, cell-free supernatants of blood mononuclear cells from healthy human donors stimulated with or without purified protein derivative of tuberculin or phytohaemagglutinin. Glucose stimulated insulin-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology.