Inflammation, Immunity and Hypertension

• Type of Material: Article
• Authors: David G Harrison, Emory University; Tomasz J. Guzik, Jagiellonian University; Heinrich Lob, Emory University; Meena Madhur, Emory University; Paul Marvar, Emory University; Salim Thabet, Emory University; Antony Vinh, Emory University; Cornelia Weyand, Stanford University
• Language: English
• Date: 2011-02
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 American Heart Association, Inc.
• Final Published Version (URL): http://hyper.ahajournals.org/content/57/2/132
• Title of Journal or Parent Work: Hypertension
• ISSN: 0194-911X
• Volume: 57
• Issue: 2
• Start Page: 132
• End Page: 140
• Grant/Funding Information: This work was supported by NIH R01HL039006, P01HL058000, P01HL095070. Drs. Marvar and Madhur were supported by NIH F32 post-doctoral fellowship grants.; Dr. Guzik was supported by the European Molecular Biology Organization Young Investigator Program and the Polish Ministry of Science and Technology.; Drs. Thabet, Lob and Vinh were supported by post-doctoral fellowships from the Amercian Heart Association.
• Keywords: cytokines; NADPH oxidase; T cell; angiotensin II; neoantigen; Interleukins
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

A prominent pathology textbook used in the United States includes an image illustrating the renal histopathology caused by malignant hypertension. The legend describes striking “onion skin” changes of a renal arteriole in the center of this figure. Curiously, a sea of mononuclear inflammatory cells surrounding this arteriole is overlooked both in the figure legend and in the related text. Moreover, nothing regarding inflammation or immune reactions is discussed. This lack of attention to inflammatory cells is, however, not surprising. While many experimental studies have implicated inflammation in hypertension, these have largely been performed in experimental animals and there is no proof that inflammation contributes to human hypertension. In fact, some anti-inflammatory or immune suppressing drugs (non-steroidal anti-inflammatory drugs and cyclosporine for example) paradoxically cause hypertension in humans, likely via off-target effects. Often the term “inflammation” is used in the context of cardiovascular disease as a catchall referring to non-specific phenomena such as elevation of C-reactive protein or the presence of macrophages in a tissue. Most clinicians and investigators find this vague and difficult to understand. Even more puzzling is that many studies now implicate the adaptive immune response, and in particular, lymphocytes in hypertension and vascular disease. Traditionally, bacterial, viral or tumor antigens activate this arm of immune defense. As such, it has been hard to imagine how adaptive immunity could be involved in a disease like hypertension. In this article, we will attempt to address some of these puzzling questions. We will briefly review components of the innate and adaptive immune response, discuss data from many groups, including our own, that suggest that common forms of hypertension are immune mediated, and provide a working hypothesis of how signals from the central nervous system trigger an immune response that causes hypertension.