Table 4.

The roles of other cytokines in atherosclerosis.

Cytokine	Summary of studies using mouse model systems	Ref.
GDF-15	Transplantation of GDF-15-deficient bone marrow in LDLr−/− model attenuates macrophage chemotaxis and accumulation, and produces a stable plaque phenotype. Deficiency in the ApoE−/− model inhibits atherosclerosis by decreasing apoptotic cells and IL-6-dependent inflammatory response to vascular injury. Transgenic overexpression in ApoE−/− model reveals a protective role.	[149], [150], [151], [152]
G-CSF	Administration in the ApoE−/− model reduces atherosclerosis (2 studies) associated with decreased serum cholesterol, increased circulating monocytes, and increased expression of IL-10 and Tregs. However, one study found increased atherosclerosis by G-CSF.	[153], [154], [155]
GM-CSF	Deficiency in the LDLr−/− model showed that it promoted advanced plaque progression by increasing macrophage apoptosis susceptibility. However, another study found reduced atherosclerosis associated with decreased content of dendritic and T-cells and disruption of elastic fibers adjacent to the lesion. Injection of viral-encoding GM-CSF in the LDLr−/− model increases atherosclerosis associated with oxidative stress, inflammation and adhesion protein expression. Deficiency in the ApoE−/− model increases lesion size associated with accumulation of macrophages and reduction in collagen content. In contrast, administration in the ApoE−/− model exacerbates atherosclerosis.	[114], [156], [157], [158]
IFN-α	Administration accelerates atherosclerosis in the LDLr−/− model.	[159]
IFN-β	Administration promotes atherosclerosis in ApoE−/− and LDLr−/− models. In contrast, the cytokine attenuated angiotensin II-accelerated atherosclerosis and vascular remodeling in ApoE−/− model.	[160], [161]
IFN-γ	Deficiency of receptor in ApoE−/− model reduces atherosclerosis lesion size and lipid accumulation, and increases collagen content. Deficiency of the cytokine attenuates atherosclerosis in ApoE−/− or LDLr−/− mice and BMT in this model reveals the importance of cytokine expressed by the hematopoietic compartment. Administration in the ApoE−/− model increases atherosclerosis associated with elevated levels of T-cells. Postnatal blocking of the function of the cytokine in the ApoE−/− model via overexpression of soluble decoy receptor prevents atherosclerotic plaque formation and stabilizes advanced plaques.	[162], [163], [164], [165], [166], [167], [168]
M-CSF	Deficiency in the ApoE−/− or LDLr−/− models attenuates atherosclerosis.	[169], [170], [171], [172]
TGF-β	Gene therapy in LDLr−/− mice reduces atherosclerosis associated with decreased oxidative stress, inflammation and adhesion protein expression. Inhibition of TGF-β signaling in the ApoE−/− model accelerates atherosclerosis associated with increased inflammation and decreased collagen content. BMT reveals the importance of the cytokine expressed by the hematopoietic compartment. Overexpression in the ApoE−/− mice reduces atherosclerosis by decreasing T-cell and macrophage content and inflammatory cytokines, and increasing collagen levels. The protective effect of estradiol on fatty streak formation in the ApoE−/− model requires TGF-β. Disruption of TGF-β signaling in dendritic and T cells affects atherosclerosis though one study found no effect in relation to T cells.	[173], [174], [175], [176], [177], [178], [179], [180], [181], [182]
TNF-α	Deficiency of the cytokine in the ApoE−/− or APOE*3-Leiden models reduces atherosclerosis associated with decreased foam cells and expression of several pro-inflammatory markers. BMT reveals important role of cytokine expressed by the hematopoietic compartment. Transplantation of bone marrow deficient in p55 TNF receptor in the LDLr−/− model reduces atherosclerosis associated with decreased foam cells and expression of pro-inflammatory markers.	[93], [183], [184], [185], [186], [187], [188], [189], [190], [191]
TNFSF12/TWEAK	Genetic deficiency/inhibition in the ApoE−/− model reduces atherosclerosis associated with diminished pro-inflammatory response and enhanced plaque stability.	[192]
TRAIL	Deficiency in the ApoE−/− model accelerates atherosclerosis, vascular calcification, diabetes and plaque instability. Systemic administration reduces atherosclerosis in this model.	[193], [194], [195], [196]