INTERLEUKIN-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, ISLET-CELL ANTIBODY,AND INSULIN-SECRETION IN CHILDREN WITH THALASSEMIA MAJOR ON LONG-TERMBLOOD-TRANSFUSION

In vitro, cytokines like interleukin-1-beta (IL-1-B) and tumour necros is factor-alpha (TNF-A) inhibit insulin release and can destroy islet B-cells. We measured blood levels of IL-1-B, TNF-A, and islet cell ant ibody (ICA) in 20 children with IDDM, 20 of their non-diabetic sibling s, 20 children with thalassemia major on long-term hypertransfusion th erapy and iron chelation, and 10 normal age-matched children, In the n on-diabetic and thalassemic children we investigated the early phase o f insulin release after i.v. glucose (0.5 g/kg, 30 per cent solution) and evaluated tolerance to oral glucose (1.75 g/kg), Circulating IL-1- B and TNF-A concentrations were significantly higher in IDDM-siblings (33.7 +/- 12.7 pg/ml and 655 +/- 165 pg/ml, respectively) v. normal ch ildren (21.1 +/- 6.4 pg/ml and 383 +/- 122 pg/ml, respectively). Thala ssemic children had no detectable circulating ICA, The prevalence of I CA was 30 per cent in children with IDDM and 60 per cent of their sibl ings. Impaired oral glucose tolerance was detected in five children wi th thalassemia (25 per cent), but in none of the IDDM-siblings, The ea rly phase of insulin release was significantly depressed in thalassemi c children (peak insulin = 29.2 +/- 5.1 mIU/ml) v. normal children (52 .3 +/- 9.5 mIU/ml) and IDDM-siblings (45.3 +/- 12.4 mIU/ml). It appear s that thalassemic children had significantly decreased insulin secret ion and impaired glucose tolerance, however, the mechanism of B-cell d ysfunction is not mediated by ICA nor by cytokines.