Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:611-616
© 1999 American Heart Association, Inc.
Original Contributions |
Expression of Interleukin-10 in Advanced Human Atherosclerotic Plaques
Relation to Inducible Nitric Oxide Synthase Expression and Cell Death
From the Institut National de la Santé et de la Recherche Médicale, IFR "Circulation Lariboisière," INSERM U 141 (Z.M., A.T.) and INSERM U 127 (C.H.), Hôpital Lariboisière, Paris, and the Service de Chirurgie Thoracique et Vasculaire (J.O., G.L.), Hôpital Beaujon, Clichy, France; and the Department of Clinical and Experimental Medicine (E.F.), University of Padova, Padova, Italy.
Correspondence to Alain Tedgui, PhD, INSERM U 141, 41 boulevard de la Chapelle, 75475 Paris Cedex 10, France.
Abstract—Inflammation is a major feature of human atherosclerosis and is central to development and progression of the disease. A variety of proinflammatory cytokines are expressed in the atherosclerotic plaque and may modulate extracellular matrix remodeling, cell proliferation, and cell death. Little is known, however, about the expression and potential role of anti-inflammatory cytokines in human atherosclerosis. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine whose expression and potential effects in advanced human atherosclerotic plaques have not been evaluated. We studied 21 advanced human atherosclerotic plaques. IL-10 expression was analyzed by use of reverse transcription–polymerase chain reaction and immunohistochemical techniques. Inducible nitric oxide synthase expression was assessed by using immunohistochemistry, and cell death was determined by use of the TUNEL method. Reverse transcription–polymerase chain reaction identified IL-10 mRNA in 12 of 17 atherosclerotic plaques. Immunohistochemical staining of serial sections and double staining identified immunoreactive IL-10 mainly in macrophages, as well as in smooth muscle cells. Consistent with its anti-inflammatory properties, high levels of IL-10 expression were associated with significant decrease in inducible nitric oxide synthase expression (P<0.0001) and cell death (P<0.0001). Hence, IL-10, a potent anti-inflammatory cytokine, is expressed in a substantial number of advanced human atherosclerotic plaques and might contribute to the modulation of the local inflammatory response and protect from excessive cell death in the plaque.
Key Words: interleukin-10 • atherosclerotic plaque • cytokines • inflammation
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