Monokine antagonism is reduced in patients with IDDM.
Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) have been implicated as immune effector molecules in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). Recently, an increased frequency of the A1/A1 genotype of an IL-1 receptor antagonist (IL-1Ra) gene polymorphism was observed in patients with IDDM. Therefore, we investigated plasma IL-1Ra and soluble TNF p55 receptor (TNFsRp55) levels in 18 men with recent-onset IDDM, 10 men with long-standing IDDM, and 35 age-matched healthy men. No differences in plasma IL-1Ra were found among the three groups. However, when the plasma IL-1Ra levels in the subjects with IDDM and the control subjects were analyzed according to IL-1Ra genotypes, we found a 30% lower level of plasma IL-1Ra in subjects with IDDM carrying the A1/A1 genotype compared with the levels in those carrying the A1/A2 genotype (372 +/- 40 vs. 530 +/- 54 ng/l, respectively, P = 0.025). In contrast, no significant association was seen between plasma IL-1Ra and IL-1Ra genotype in the control subjects. The TNFsRp55 level in heparinized plasma was 17% lower in patients with IDDM than in control subjects (3.93 +/- 0.22 vs. 4.72 +/- 0.24 micrograms/l, respectively, P = 0.038). These findings could not be explained by metabolic derangement in the IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Mandrup-Poulsen
T
T
Steno Diabetes Center, Gentofte, Denmark.
Pociot
F
F
Mølvig
J
J
Shapiro
L
L
Nilsson
P
P
Emdal
T
T
Røder
M
M
Kjems
L L
LL
Dinarello
C A
CA
Nerup
J
J
D000328:Adult; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007958:Leukocyte Count; D008297:Male; D008969:Molecular Sequence Data; D015846:Monokines / Q000037:antagonists & inhibitors*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011863:Radioimmunoassay; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D012016:Reference Values; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics
D001786:Blood Glucose; D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015846:Monokines; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins