Unraveling the Role and Complexities of Inflammation in Hypertension.

Abstract

See related article, pp 839–845 Expression and activation of inflammatory genes and pathways have been linked to several cardiovascular diseases, such as atherosclerosis, diabetes mellitus, and high blood pressure. For example, genetic deficiency of proinflammatory cytokines, such as IL-6 (interleukin-6), IL-17, and TNFα (tumor necrosis factor-α), are associated with a blunting or lessening of the pressor response produced by angiotensin II infusion alone or in combination with a high-salt diet.1–3 Similarly, the absence of T and B lymphocytes is also associated with reductions in the hypertension produced by angiotensin II.4 Taken together, such experimental and genetic findings provide strong evidence that inflammatory gene products contribute to the development and maintenance of hypertension. Because inflammation is a finely orchestrated process involving activation of several inflammatory pathways, it stands to reason why most studies have focused on the contribution played by proinflammatory cytokines in hypertension. Although much emphasis has been devoted to uncovering the contribution of proinflammatory cytokines, much less is known about the role of anti-inflammatory molecules in regulation of blood pressure in general or the development of hypertension. Equally important as activation of inflammatory pathways is inhibition or suppression of inflammation to promote resolution of inflammation and limit tissue injury. Better understanding of the role played by anti-inflammatory cytokines can potentially lead to exploitation of these molecules as clinical therapies. IL-10 is a major anti-inflammatory cytokine belonging to the eponymous IL-10 family of cytokines, which includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26.5 The IL-10 family shares several structural and receptor similarities, and each IL-10 family member displays unique biological properties. IL-10 is considered the most potent anti-inflammatory cytokine of the group and exerts most of its effects, namely functional suppression of immune signaling, on monocytes and macrophages. Other important effects of IL-10 include inhibition …