title: Release of TNF-alpha from in vitro-stimulated monocytes is negatively associated with serum levels of apolipoprotein B in patients with type 2 diabetes.
abstract: Impaired course of inflammation is a likely mechanism behind a number of diabetic complications. The present study was undertaken to investigate lipopolysaccharide-induced production of tumour necrosis factor (TNF)-alpha in monocytes from patients with type 2 diabetes and to assess its relationship with diabetes-associated metabolic abnormalities. Monocytic TNF-alpha mRNA production was lower in the diabetic participants compared to their corresponding controls. Diabetic subjects who had been receiving simvastatin treatment had TNF-alpha mRNA production similar to that of the healthy participants. The release of TNF-alpha from diabetic cells correlated negatively with serum levels of apolipoprotein B (apoB) (R = -0.755, P = 0.001), total plasma cholesterol (R = - 0.702, P = 0.002) and the presence of retinopathy (R = -0.572, P = 0.021). No such associations were found in the control subjects. In a multiple linear regression model, only the level of apoB and diabetes duration demonstrated significant effects on the release of TNF-alpha, with apoB alone accounting for 57% of the variation. We conclude that production of TNF-alpha mRNA in response to the bacterial stimulant is compromised in poorly controlled type 2 diabetes. Lipid abnormalities are associated with the observed defect. Impaired cytokine production represents a significant defect in the functioning of the immune system and may contribute to aberrations in the course of inflammation in the diabetic state.
authors.affiliation: Medical Faculty, University of Tromsoe, Norway. svetlana@fagmed.uit.no
authors.forename: S N
authors.initials: SN
authors.lastname: Zykova
authors.forename: J
authors.initials: J
authors.lastname: Svartberg
authors.forename: R
authors.initials: R
authors.lastname: Seljelid
authors.forename: H
authors.initials: H
authors.lastname: Iversen
authors.forename: A
authors.initials: A
authors.lastname: Lund
authors.forename: D N
authors.initials: DN
authors.lastname: Svistounov
authors.forename: T G
authors.initials: TG
authors.lastname: Jenssen
mesh_terms: D001055:Apolipoproteins B / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha