Interaction of lnterleukin-1 With Islet β-Cells: Distinction Between Indirect, Aspecific Cytotoxicity and Direct, Specific Functional Suppression

A 5-day culture of adult rat islets with human recombinant IL-1β (3 U/ml) resulted in the death of most oc-cells and 50% of β-cells. The IL-1-exposed islet tissue contained—in addition to poorly granulated β-cells—patches of outgrowing monolayers and dispersed activated macrophages. In purified α- and β-cell preparations, no cytodestructive effects of IL-1 (as high as 30 U/ml) were noticed, indicating that the cytokine is in itself not a β-cell-selective killer. Pure β-cells were, on the other hand, more sensitive (from 0.3 U/ml on) than intact islets to an IL-1-induced suppression of hormone synthesis. This inhibitory action was reversible and affected predominantly the production of insulin, leading to degranulated cells with modified shape and attachment. Further studies with IL-1 should take into account that isolated islet preparations do not allow distinction between its irreversible, indirect, and aspecific β-cell toxicity and its reversible, direct, and specific suppression of β-cell functions. It is not yet known whether IL-1-suppressed β-cells exhibit an altered sensitivity to β-cell-toxic conditions.