IN-VITRO SECRETION OF INTERLEUKIN-1-BETA AND INTERFERON-GAMMA BY PERIPHERAL-BLOOD LYMPHOMONONUCLEAR CELLS IN DIABETIC-PATIENTS

There is evidence that cytokines, in particular interleukin-1 beta (IL -1 beta) and interferon-gamma (IFN-gamma) might mediate beta cell dest ruction 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 phy tohaemagglutinin (PHA) in 33 diabetic patients and in 10 normal contro ls. 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) typ e 1 diabetics with duration of the disease between 2 years and 10 year s; and Group 4, 10 type 2 diabetics). No difference was found among th e 4 groups considered in IL-1 beta secretion by unstimulated cultures, although the percentage of TAC+ cells was significantly higher in typ e 1 newly diagnosed diabetic patients with respect to the LS, the type 2 diabetics and the controls. After PHA stimulation a significant inc rease of IL-1 beta was found in newly diagnosed type 1 diabetic patien ts in comparison with the control subjects, the LS and type 2 diabetic patients (P < 0.001). The supernatants of newly diagnosed type 1 diab etics also showed a significant reduction in IFN-gamma production both in basal (P < 0.01) and in stimulated conditions (P < 0.001) in compa rison 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 bot h in basal and stimulated conditions). No correlation was found betwee n lymphokine production levels and age, sex and metabolic control para meters, i.e daily mean glycemia and HbA(1c) levels. Our data suggest a dysregulation in the lymphokine cascade in the diabetic disease, rest ricted to the early stage of type 1 diabetes.