Secretion Of Pro-inflammatory Cytokines By Activated T Cells Cultured In Pvat-conditioned Media From Dahl S Rats On A High Fat Diet Occurs Early During Development Of Hypertension

There is considerable evidence for a role for the immune system in the development of hypertension, however the exact nature of this role is currently being characterized. Specifically, T cells have been identified as one of the immune cell types that contributes to hypertension. Our previous studies demonstrated that mesenteric perivascular adipose tissue (mPVAT) harbors a large T cell population. In the present study, we tested the hypothesis that soluble mediators in mPVAT influence T cell function during hypertension. Toward this end, we utilized a unique model of hypertension in which Dahl S rats on a high fat/high calorie diet develop hypertension by 17 weeks of age, whereas Dahl S rats on normal rodent chow do not. We found that conditioned media from mPVAT from Dahl S rats on a high fat diet markedly increased activated T cell production of the pro-inflammatory cytokines, GM-CSF, IFNγ and IL-17a as compared to cytokine production by T cells cultured in mPVAT-conditioned media from rats on normal control chow (Table 1). These cytokines would be expected to cause pleiotropic inflammatory effects, including increasing the numbers and activation of macrophages and neutrophils, among other effects. Conversely, the anti-inflammatory cytokine, IL-10, was not different between the groups, suggesting the effect is selective for inflammatory cytokines. Taken together, these data strongly suggest soluble mediators from PVAT influence T cell inflammatory status early during the development of hypertension triggered by high fat diet. Overall, the data provide evidence for a role for T cells in high fat diet-associated hypertension. (This study was supported by NIH grant P01 HL070687)