Immunosuppression in Atherosclerosis

Abstract

An estimated 1014 microbes live on our mucosal surfaces, exceeding by far the number of cells in our body (approximately 1013). Survival depends on our ability to recognize, wall off, and eliminate unwanted intruders. The doubling of life expectancy over the last century has created an internal burden of degenerating tissue, cellular debris, and malignant transformation, adding considerable stress to host defense mechanisms. The most powerful protective tool that we have is inflammation, a generic response pattern that allows the immune system to rapidly recognize threats, mobilize cells to injury sites, remove instigators, and heal wounds. Articles pp 1968 and 1977 Acute inflammation is short-lived and characterized by the recruitment of polymorphonuclear granulocytes followed by monocytes. Inflammation is self-amplifying and intensified through the sequential release of lipid mediators, cytokines, and chemokines. By 48 to 72 hours, granulocytes are replaced by lymphocytes. Despite the domino effect of a few inflammatory cells recruiting millions of others, inflammation is usually self-limited, resolving within days to weeks. If not, the response switches to chronic mode. Lymphocytes then dominate the force of inflammatory cells, and new rules dictate cell-cell communication, collateral damage, and repair. Most diseases categorized as chronic inflammatory disorders persist over decades, bringing a much greater time dimension to the inflammatory process. Although atherosclerosis is a quintessential chronic, persistent inflammatory disease,1 it differs from most others because its smoldering disease activity lasts for 30 to 70 years. Obviously, the mechanisms of acute and chronic inflammation are distinct; granulocytes and lymphocytes utilize fundamentally different means to recognize danger and react. Neutrophils, which live only for hours and generate no memory of their engagement with harmful substances, sense microbial and nonmicrobial danger signals through inherited receptors that are similar in all hosts. Lymphocytes, however, are long-lived cells; some survive for decades and …