Interleukin 18 and Cardiovascular Disease in HIV-1 Infection: A Partner in Crime?

Cardiovascular disease has been frequent in HIV-infected patients both before and after the advent ofantiretroviral therapy (HAART). The pathogenic basis for the increase of cardiovascular disease, inparticular myocardial lesions, may involve HIV-1 itself or other mechanisms including endothelial dysfunction,activation of proinflammatory cytokines, and changes in platelets, which lead to atherosclerotic lesionsof blood vessels. In the last decade, among the proinflammatory cytokines, interleukin 18 seems toplay a central role in the inflammatory cascade, leading to development of atherosclerotic disease andthe occurrence of ischemic heart disease in uninfected HIV-1 people. Increased levels of interleukin18 were observed in HIV-1 infected patients.This review attempts to evaluate the role of interleukin 18 in cardiovascular disease, especially in myocardialinfarction, in HIV-1 infection, as well as the relationship between interleukin 18 and atheroscleroticplaque formation.Two other characteristic aspects in HIV-1 infection, metabolic syndrome and lipodystrophy, will beevaluated in light of activity of interleukin 18. Moreover, the role of platelets and interleukin 18 as animportant linkage between chronic inflammation, endothelial dysfunction, and atherogenesis will be highlighted.Finally, experimental an animal model of rhesus macaques infected with simian immunodeficiency virusclearly demonstrates the involvement of interleukin 18 in myocardial lesions, and that circulating levelsof interleukin 18 are important predictors of coronary heart disease.In conclusion, interleukin 18 may be considered a partner in crime with other factors, includingendothelial dysfunction, increased expression and production of adhesion molecules and proinflammatorycytokines in determining cardiovascular disease.