Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction--a novel mechanism for maintaining vascular function

Abstract

Endothelial dysfunction is a pathological status of the vascular system, which can be broadly defined as an imbalance between endothelium-dependent vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the progression of many pathological processes including atherosclerosis, type II diabetes and hypertension. Previous reports have demonstrated that pro-inflammatory/immunoeffector cytokines significantly promote endothelial dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines have recently been identified such as interleukin (IL)-35. However, the effects of anti-inflammatory cytokines on endothelial dysfunction have received much less attention. In this analytical review, we focus on the recent progress attained in characterizing the direct and indirect effects of anti-inflammatory/immunosuppressive cytokines in the inhibition of endothelial dysfunction. Our analyses are not only limited to the importance of endothelial dysfunction in cardiovascular disease progression, but also expand into the molecular mechanisms and pathways underlying the inhibition of endothelial dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.

Figure 1

A new working model: Regulatory T cells and immunosuppressive/anti-inflammatory cytokines inhibit endothelial dysfunction. In physiological status, the interaction between endothelium-dependent vasoconstrictors (including Ang II, ET-1, ROS) and vasodilators (NO, EDHF and PGI2) maintain the endothelial function and equilibrium of vascular tone. The impairment of the balance between the vasoconstrictors and vasodilators is generally defined as the endothelial dysfunction. Under cardiovascular diseases risk factors stimuli, when vasodilation pathways being impaired or vasoconstriction being activated, endothelial dysfunction occurs. Regulatory T cells (Tregs) act on endothelial cells via cell-cell-interaction and/or immunosuppressive/antiinflammatory cytokines to inhibit endothelial dysfunction and restore normal vascular tone.