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April 1998
Chemokines -- Chemotactic Cytokines That Mediate Inflammation
Andrew D. Luster, MD, PhD; The New England Journal of Medicine,February 12,1998; Vol. 338, No. 7,1998, pg 436-444.
No abstract available
Inflammation is central to many diseases and conditions related directly to anesthesiology, critical care medicine, and perioperative care. Research in this field has made great strides in helping to dissect the general process of inflammation into increasingly detailed components and regulatory processes, each potentially offering specific avenues for prevention and intervention in various disease states. Even definitions of conditions associated with inflammation have undergone considerable evolution (American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients by D.J.J. Muckart, MBChB, FRCS and S.Bhagwanjee, MBChB, FCA, Critical Care Medicine, Vol. 25, No. 11, pg 1789-1795). Further, the array of endogenous substances associated with the inflammatory process has grown significantly in number and complexity.
The practitioner can meet a bewildering number of "mediators of inflammation", each of which tends to be labeled with non-intuitive names and associated with novel cellular functions. Despite the sense of helplessness the clinician may feel in the midst of this explosion of new information regarding mediators of inflammation, it is important to appreciate, at least in general terms, the rapid development of new, specific information in this important field, and the potential value of this knowledge in therapy.
The author provides a well-written, current update of mechanisms of disease and inflammatory mediators. It begins with the well-known premise that the attraction of leukocytes to tissues is essential for inflammation and the host response to infection. This review emphasizes the role of chemokines (chemotactic cytokines), a family of cytokines that are only beginning to be fully understood in the context of the regulation of the inflammatory process. Over 40 chemokines have been identified to date, most of them in recent years. As suggested above, the relationships among chemokines were not initially appreciated, leading to confusing nomenclature and an initial lack of understanding of coordinated biologic activity. This article provides a useful figure relating cell type, the chemokines associated with each cell type, and the nature of related chemokine receptors. This list includes chemokines identified for the following cell types: eosinophil, basophil, monocyte, activated T-cell, resting T-cell, dendrictic cell, neutrophil and natural killer cell.
Chemokines are thought to play an important role in leukocyte movement and function. The movement of leukocytes from blood into tissues is a regulated multi-step process involving a series of coordinated interactions between leukocytes and endothelial cells. Cellular regulators such as selectins, integrins and chemokines are thought to control different aspects of this important process. These terms are increasingly introduced in current literature relating to inflammatory disease. "Selectins" facilitate the movement of leukocytes ("rolling") along the surface of endothelial cells. "Chemokines" provide signals that convert selectin-mediated interactions into purposeful extravasation of leukocytes mediated by "integrins."
The author asks an important fundamental question: "If pro-inflammatory cytokines stimulate secretion of many of the same chemokines, how can an inflammatory response be specific? In asthma, for example, eosinophils accumulate in the airways, whereas the host response to bacterial pneumonia is dominated by neutrophils." The example raised in this question highlights the point that the recruitment of leukocytes into tissues is a multi-step process in which chemokines participate, but do not act alone. It is likely that chemokines act jointly with other cytokines to cause tissue infiltration as well as increasing the responsiveness of leukocytes to a chemokine.
Finally, the author offers a very interesting description of the role of chemokines in current concepts regarding inflammatory disease processes. He provides some very useful conceptual diagrams of the complex process of regulation of leukocyte movement, their role in inflammatory diseases, the characteristic cellular infiltrates associated with these diseases, and known chemokines involved. Diseases considered in this context include sarcoidosis, glomerulonephritis, arthritis, atherosclerosis, adult respiratory distress syndrome, asthma, psoriasis, and bacterial and viral meningitis.
The background provided in this article assists us in beginning to appreciate the important roles of chemokines in the pathophysiology of disease, and how this knowledge may be of value in current and future treatment strategies.
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