Protective Effects of Angiotensin II Interruption: Evidence for Antiinflammatory Actions

Nigel J. Dagenais, B.Sc.(Pharm.); Fakhreddin Jamali, Ph.D.


Pharmacotherapy. 2005;25(9):1213-1229. 

In This Article

Cytokines and Inflammatory Mediators

Cytokines are a group of small proteins and polypeptides produced and secreted throughout the body. They are involved in immune function, inflammation, tissue repair, cell growth, and normal physiologic processes such as sleep regulation.[3,13] Altered cytokine expression often signifies emergence of a symptom or disease.[13] Although cytokines usually act locally in a paracrine manner, affecting adjacent cells, they may also act intracellularly, travel distally through circulation in an endocrine fashion, or act within the same cell after release.[14]

As a common rule, cytokines have either proinflammatory or antiinflammatory properties. However, they cannot be clearly divided into distinct categories because their effects often overlap.[3] However, in this article, the proinflammatory mediators will be considered the culprits in atherosclerosis and autoimmune disease. These mediators are closely associated with elevated risk of cardiovascular disease and progression of disease in patients with rheumatoid arthritis.[10,11,12,13,14,15,16] Conversely, the antiinflammatory mediators discussed in this article are considered beneficial for patients with cardiovascular disease and rheumatoid arthritis, since these mediators suppress proinflammatory mediator production.[3,16]

The cytokines interleukin (IL)-1, IL-2, IL-12; tumor-necrosis factor (TNF)-α; and interferon (IFN)-γ are generally considered proinflammatory, whereas IL-4 and IL-10 are typically antiinflammatory.[3,15] Transforming growth factor (TGF)-β is unique because when secreted early in immune response, it appears to evoke anti-inflammatory characteristics, but once disease is established, it leads to progressive organ fibrosis.[4] Transforming growth factor-β is implicated as an important proinflammatory mediator in cardiac remodeling and heart failure after myocardial infarct.[17]

Another marker of inflammation is C-reactive protein, a major component of the acute-phase response. The cytokine IL-6 seems to be involved in regulating this acute-phase process and has numerous functions in the body, many of which are proinflammatory.[18] In addition, the chemokines and cell adhesion molecules—such as monocyte chemotactic protein-1, vascular cell adhesion molecule, endothelial leukocyte adhesion molecule, intracellular adhesion molecule, and the selectins—represent other relevant indicators of inflammation. These molecules are critical in attracting and adhering circulating leukocytes to the inflammation site, and they may play a pivotal role in starting the inflammatory process.[10,11,12,14,16]