Pancreatic beta-cell function and interleukin-1 beta in plasma during the acute phase response in patients with major burn injuries.
Animal experiments demonstrate that interleukin-1 beta (IL-1 beta) is beta-cell cytotoxic in vitro and inhibits insulin secretion in vivo. However, it is unknown if IL-1 beta affects beta-cell function in man. Since IL-1 beta and other cytokines are main mediators of the acute phase response, the objectives of the present study were to examine beta-cell function in patients with major burn injuries, and to test if changes in beta-cell function correlated to systemic levels of IL-1 beta and tumour necrosis factor alpha (TNF alpha). We established and validated an IL-1 beta assay measuring free and protein bound IL-1 beta; protein bound IL-1 beta was detached from the IL-1 beta specific binding protein by acidification, rendering it accessible for the employed antibody. The IL-1 beta specific binding protein (43-60 kDa) was found in serum and plasma from all tested patients and normal subjects. Survivors of burn injuries had a stimulated beta-cell function, whereas non-survivors had an impaired beta-cell function as indicated by an increased plasma concentration of proinsulin, and an increased proinsulin/insulin ratio. In addition, non-survivors had significantly increased plasma levels of IL-1 beta. However, we could not demonstrate any correlation between C-peptide, proinsulin, insulin or proinsulin/insulin ratio and plasma concentration of IL-1 beta. In conclusion, beta-cell function abnormalities are evident in patients with major burn injuries, and a high plasma level of IL-1 beta correlates with a fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Wogensen
L
L
Steno Diabetes Center, Gentofte, Denmark.
Jensen
M
M
Svensson
P
P
Worsaae
H
H
Welinder
B
B
Nerup
J
J
D000210:Acute-Phase Reaction / Q000097:blood / Q000503:physiopathology; D000328:Adult; D002056:Burns / Q000097:blood / Q000503:physiopathology*; D002096:C-Peptide / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000097:blood*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011384:Proinsulin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002096:C-Peptide; D002352:Carrier Proteins; D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011384:Proinsulin