Tumor necrosis factor-alpha does not mediate diabetes-induced vascular inflammation in mice.
OBJECTIVE
Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF) alpha as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF alpha in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice.


RESULTS
Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries 150 m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF alpha-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF alpha -/- mice, whereas no such effects were observed in C57BL/6 wild-type mice.


CONCLUSIONS
The present findings suggest that TNF alpha does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF alpha. These effects are partly attributable to a direct antiinflammatory role of TNF alpha, but may also reflect a defective development of the immune system in these mice.
Nilsson-Ohman
Jenny
J
Department of Clinical Sciences, Malmö University Hospital, Malmö, Sweden.
Fredrikson
Gunilla Nordin
GN
Nilsson-Berglund
Lisa M
LM
Gustavsson
Carin
C
Bengtsson
Eva
E
Smith
Maj-Lis
ML
Agardh
Carl-David
CD
Agardh
Elisabet
E
Jovinge
Stefan
S
Gomez
Maria F
MF
Nilsson
Jan
J
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D002536:Cerebral Arteries / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology*; D007249:Inflammation / Q000209:etiology*; D008077:Lipoproteins, LDL / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D001057:Apolipoproteins E; D001323:Autoantibodies; D001786:Blood Glucose; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D013311:Streptozocin