In vitro secretion of interleukin-1β and interferon-γ by peripheral blood lymphomononuclear cells in diabetic patients

Abstract

There is evidence that cytokines, in particular interleukin-1β (IL-1gb) and interferon-γ (IFN-γ) might mediate β cell destruction in type 1 diabetes. Therefore the secretion of these cytokines by peripheral blood lymphomononuclear cells (PBMNC) was investigated in basal conditions and 48 h after stimulation with T-cell mitogen phytohaemagglutinin (PHA) in 33 diabetic patients and in 10 normal controls. The patients were divided in 4 groups (Group 1, 10 controls; Group 2, 13 newly diagnosed type 1 diabetics, the onset had occurred from 5 days to 3 months before the study; Group 3, 10 Long Standing (LS) type 1 diabetics with duration of the disease between 2 years and 10 years; and Group 4, 10 type 2 diabetics). No difference was found among the 4 groups considered in IL-1β secretion by unstimulated cultures, although the percentage of TAC+ cells was significantly higher in type 1 newly diagnosed diabetic patients with respect to the LS, the type 2 diabetics and the controls. After PHA stimulation a significant increase of IL-1β was found in newly diagnosed type 1 diabetic patients in comparison with the control subjects, the LS and type 2 diabetic patients ( P < 0.001). The supernatants of newly diagnosed type 1 diabetics also showed a significant reduction in IFN-γ production both in basal ( P < 0.01) and in stimulated conditions ( P < 0.001) in comparison with the controls, the LS ( P < 0.002 in basal, and P < 0.001 in stimulated conditions) and the type 2 diabetic patients ( P < 0.001 both in basal and stimulated conditions). No correlation was found between lymphokine production levels and age, sex and metabolic control parameters, i.e daily mean glycemia and HbA 1c levels. Our data suggest a dysregulation in the lymphokine cascade in the diabetic disease, restricted to the early stage of type 1 diabetes.