PANCREATIC BETA-CELL FUNCTION AND INTERLEUKIN-1-BETA IN PLASMA DURINGTHE ACUTE-PHASE RESPONSE IN PATIENTS WITH MAJOR BURN INJURIES

Animal experiments demonstrate that interleukin-1beta (IL-1beta) is be ta-cell cytotoxic in vitro and inhibits insulin secretion in vivo. How ever, it is unknown if IL-1beta affects beta-cell function in man. Sin ce IL-1beta and other cytokines are main mediators of the acute phase response, the objectives of the present study were to examine beta-cel l function in patients with major burn injuries, and to test if change s in beta-cell function correlated to systemic levels of IL-1beta and tumour necrosis factor alpha (TNFalpha). We established and validated an IL-1beta assay measuring free and protein bound IL-1beta; protein b ound IL-1beta was detached from the IL-1beta specific binding protein by acidification, rendering it accessible for the employed antibody. T he IL-1beta specific binding protein (43-60 kDa) was found in serum an d plasma from all tested patients and normal subjects. Survivors of bu rn injuries had a stimulated beta-cell function, whereas non-survivors had an impaired beta-cell function as indicated by an increased plasm a concentration of proinsulin, and an increased proinsulin/insulin rat io. In addition, non-survivors had significantly increased plasma leve ls of IL-1beta. However, we could not demonstrate any correlation betw een C-peptide, proinsulin, insulin or proinsulin/insulin ratio and pla sma concentration of IL-1beta. In conclusion, beta-cell function abnor malities are evident in patients with major burn injuries, and a high plasma level of IL-1beta correlates with a fatal outcome. However, the present study did not provide evidence for the hypothesis that beta-c ell function is influenced by circulating IL-1beta or TNFalpha during the acute phase response.