title: Cytokines and atherosclerosis: a comprehensive review of studies in mice.
abstract: In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are monocyte-derived macrophages and T-lymphocytes. Both cell types produce a wide array of soluble inflammatory mediators (cytokines, chemokines) which are critically important in the initiation and perpetuation of the disease. This review summarizes the currently available information from mouse studies on the contribution of a specified group of cytokines expressed in atherosclerotic lesions, viz. interleukins (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, IL-20) and macrophage-associated cytokines [tumour necrosis factor-alpha (TNF-alpha); macrophage migration inhibitory factor (MIF); interferon-gamma (IFN-gamma); colony stimulating factors G-CSF,-M-CSF,-GM-CSF) to atherogenesis. Emphasis is put on the consistency of the effects of these cytokines, i.e. inasmuch an effect depends on the experimental approach applied (overexpression/deletion, strain, gender, dietary conditions, and disease stage). An important outcome of this survey is (i) that only for a few cytokines there is sufficient consistent data allowing classifying them as typically proatherogenic (IL-1, IL-12, IL-18, MIF, IFN-gamma, TNF-alpha, and M-CSF) or antiatherogenic (IL-10) and (ii) that some cytokines (IL-4, IL-6 and GM-CSF) can exert pro- or anti-atherogenic effects depending on the experimental conditions. This knowledge can be used for improved early detection, prevention and treatment of atherosclerosis.
authors.affiliation: TNO-BioSciences, Gaubius-Laboratory, Department of Vascular and Metabolic Diseases, PO Box 2215, 2301 CE Leiden, The Netherlands. robert.kleemann@tno.nl
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.forename: Susanne
authors.initials: S
authors.lastname: Zadelaar
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D003115:Colony-Stimulating Factors / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003115:Colony-Stimulating Factors; D016207:Cytokines; D007378:Interleukins; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma