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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1465.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Tumor Necrosis Factor- Does Not Mediate Diabetes-Induced Vascular Inflammation in Mice

Jenny Nilsson-Öhman; Gunilla Nordin Fredrikson; Lisa M. Nilsson-Berglund; Carin Gustavsson; Eva Bengtsson; Maj-Lis Smith; Carl-David Agardh; Elisabet Agardh; Stefan Jovinge; Maria F. Gomez; Jan Nilsson

From the Department of Clinical Sciences (J.N.-O., G.N.F., L.M.N.-B., C.G., E.B., M.-L.S., C.-D.A., E.A., M.F.G., J.N.), Malmö University Hospital, Lund University; the Department of Biomedical Laboratory Science (G.N.F.), Malmö University; and the Department of Clinical Sciences (S.J.), Lund University Hospital, Lund University, Sweden.

Correspondence to Jan Nilsson, CRC Entrance 72, 91:12, Malmö University Hospital, SE-205 02 Malmö, Sweden. E-mail jan.nilsson{at}med.lu.se

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) as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE^–/– mice.

Methods and Results— Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries >150 µm 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-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^–/– mice, whereas no such effects were observed in C57BL/6 wild-type mice.

Conclusions— The present findings suggest that TNF does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF. These effects are partly attributable to a direct antiinflammatory role of TNF, but may also reflect a defective development of the immune system in these mice.

Using C57BL/6 wild-type and apoE^–/– mice deficient for TNF we demonstrate that TNF does not mediate vascular inflammation in response to streptozotocin-induced hyperglycemia. We also report evidence for a dysregulation of vascular inflammation in TNF^–/– mice revealing an unexpected protective role for this cytokine.

Key Words: diabetes • inflammation • atherosclerosis • tumor necrosis factor