@article{468939f0aa9d11dfb62d000ea68e967b,
title = "Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes",
abstract = "Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1\% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5\% in the type 2 diabetic patients and 1\% in the controls (odds ratio 2.5, 95\% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6 were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5\% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when challenged with a high-fat diet. Mice with very high plasma levels of aAb-IL6 developed elevated fasting plasma glucose (mM, 4.8+/-0.4 vs 3.3+/-0.1, P<0.001) and impaired glucose tolerance (AUC glucose, 1340+/-38 vs 916+/-25, P<0.001) as compared with sham-control mice on normal chow. In conclusion, the prevalence of plasma aAb-IL6 at levels known to impair IL6 signaling in vivo is increased 2.5-fold in people with type 2 diabetes. In mice, matching levels of aAb-IL6 cause obesity and hyperglycemia. These data suggest that a small subset of type 2 diabetes may in part evolve from an autoimmune attack against IL6.",
keywords = "Adult, Aged, Animals, Autoantibodies, Case-Control Studies, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Interleukin-6, Male, Mice, Mice, Inbred DBA, Middle Aged",
author = "K Fosgerau and P Galle and Torben Hansen and A Albrechtsen and Rieper, \{C de Lemos\} and Pedersen, \{B Klarlund\} and Larsen, \{L Kongskov\} and Thomsen, \{A Randrup\} and O Pedersen and Hansen, \{M Bagge\} and A Steensberg",
year = "2010",
month = mar,
day = "1",
doi = "10.1677/JOE-09-0413",
language = "English",
volume = "204",
pages = "265--73",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "BioScientifica Ltd.",
number = "3",
}