Cytokines in atherosclerosis: an intricate balance

Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as important mediators, is essential throughout all stages of atherosclerosis development and progression. It is known that an inflammatory imbalance is present in atherosclerosis, where numerous pro-inflammatory cytokines such as IFNγ are known to promote atherosclerosis development, while anti-inflammatory cytokines like IL-10 are considered to be anti-atherogenic in general. Many experimental atherosclerosis studies have indeed shown that modulation of pro-inflammatory cytokines reduces atherosclerotic lesion size and severity, and vice versa for the anti-inflammatory cytokines. As the inflammatory response is crucial for atherogenesis, modulation of inflammation will be of value in the search for new atherosclerosis therapies. Therefore, in this thesis the role of the interferons and of IL-10 in the immune response in atherosclerosis was studied by the use of treatment and myeloid specific knockout models. Additionally, the functional contribution of interferons in atherogenesis with regards to foam cell formation and foam cell inflammatory responses was assessed. This thesis provides the interferons and IL-10 as novel targets to influence the immunological imbalance in atherosclerosis. However, further characterization of these potential targets is still required to determine their clinical feasibility as atherosclerosis treatment.