Expression of interleukin-10 in advanced human atherosclerotic plaques - Relation to inducible nitric oxide synthase expression and cell death

Inflammation is a major feature of human atherosclerosis and is central to development and progression of the disease. A variety of proinflammatory cy tokines are expressed in the atherosclerotic plaque and may modulate extrac ellular matrix remodeling, cell proliferation, and cell death. Little is kn own, however, about the expression and potential role of anti-inflammatory cytokines in human atherosclerosis. Interleukin-10 (IL-10) is a major antii nflammatory cytokine whose expression and potential effects in advanced hum an atherosclerotic plaques have not been evaluated. We studied 21 advanced human atherosclerotic plaques. IL-10 expression was analyzed by use of reve rse transcription-polymerase chain reaction and immunohistochemical techniq ues. Inducible nitric oxide synthase expression was assessed by using immun ohistochemistry, 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 sect ions and double staining identified immunoreactive IL-10 mainly in macropha ges, as well as in smooth muscle cells. Consistent with its anti-inflammato ry properties, high levels of IL-10 expression were associated with signifi cant decrease in inducible nitric oxide synthase expression (P<0.0001) and cell death (P<0.0001). Hence, IL-10, a potent anti-inflammatory cytokine, i s expressed in a substantial number of advanced human atherosclerotic plaqu es and might contribute to the modulation of the local inflammatory respons e and protect from excessive cell death in the plaque.