Table 1. Cytokines and chemokines.

Target	Treatment	Immunological/metabolic effect	Effect on atherosclerosis	Experimental model	Diet	Reference
TNF α	Chimeric sTNF-RI/Fc (pellets)	Combined inhibition of TNF-α and LT-α, tendency of ↑TC	75% ↓ in lesion size, ↑ in CD3+ stained area in the plaques	Male apoE−/− mice	Normal chow diet	Branen et al., 2004 [64]
IL-12	Immunization with IL-12–PADRE complex	Blocking endogenous IL-12 function by induction of anti IL-12 Abs (IgG1, IgG2a), ↓ serum IFN-γ	69% ↓ in intima area, 67% ↓ intima/media ratio, 58% ↓ in the amount of stenosis, 4-fold ↑ in SMCs, 3-fold ↑ in collagen content, ↓ IFN-γ+ cells	Female LDLR−/− mice (bilateral CA collar)	Western type diet	Hauer et al., 2005 [65]
CCL5/RANTES receptor	Met RANTES (RANTES receptor antagonist)	Limits monocyte/macrophage and T-cell chemotaxis and T-cell activation by blocking RANTES signalling	43% ↓ aortic root, 58% ↓ thoraco-abdominal aorta, 43% ↓ Mac-1+, 83% ↓ CD4+, ↑ SMCs and collagen, ↓ MMP-9 expression, ↓ CCR5 and CCR2 mRNA expression	Male LDLR−/− mice	High chelesterol diet	Veillard et al., 2004 [66]
MIF	Anti-MIF monoclonal antibody	Neutralization of MIF, ↑ serum IL-2, IL-4, IL-6, IL-10 and TNFα	↓ Mac-1+ cells (26% vs. 52%), ↓ Mac-2+ foam cells, ↑ αSMA (44% vs. 23%), ↑ neointimal collagen type I (28% vs. 16%)	Female apoE−/−, (wire induced injury in left CA)	Atherogenic diet	Schober et al., 2004 [67]
MIF	Anti-MIF monoclonal antibody	Neutralization of MIF, ↓ serum MIF, ↓ serum IL-6, ↓ fibrinogen	Small non-significant ↓ in aortic plaque, ↓ mRNA expression of ICAM-1, MMP-2, TNF and IL-12, ↓ protein expression of CD40L, phospho-c-Jun and C/EBPβ	apoE−/− mice	Normal chow diet	Burger-Kentischer et al., 2006 [68]
MIF	Anti-MIF monoclonal antibody	Neutralization of MIF, blockage MIF/CXCR2 interaction	Regression of pre-existing atherosclerotic plaques (aortic root), ↓ macrophages and CD3+ T-cells	apoE−/− mice	Atherogenic diet	Bernhagen et al., 2007 [69]
CCR5 and CXCR3	HIV entry inhibitor, TAK-779 (CCR5 and CXCR3 antagonist)	Antagonism of CCR5 and CXCR3, CD4+ T-cells (↓ in blood and lymph nodes; ↑ in spleen), CD8+ T-cells (↓ in blood and lymph nodes), ↑ mRNA of CCR5, CCR2, MCP-1, IL-12, IL-4 in spleen	68% ↓ carotid lesion size, 49% ↓ intima-media ratio, 56% ↓ intima lumen ratio, 95% ↓ CD3+ T-cells, 98% ↓ INF-γ+ area	Female LDLR−/− mice (CA collar)	Western type diet	Van Wanrooij et al., 2005 [70]
CXCR3	NBI-74330 (CXCR3 antagonist)	Antagonism of CXCR3, 64% ↓ cell numbers in draining lymph nodes (with ↑ of CD4+CD25high, ↑ CD4+CD62Lhigh)	↓ Lesion size (27% ↓ in aortic root, 53% ↓ in aorta), ↑ TGF-β+ area, ↑ mRNA expression of Foxp3,CD25, CTLA-4 (in carotid artery)	Female LDLR−/− mice	Western type diet	Van Wanrooij et al., 2008 [71]
RANTES	Inhibitor of endogenous RANTES [44MNA47]-RANTES	Inhibition of RANTES, ↓ leukocyte rolling and arrest in mesenteric, vessels, ↓ secretion of IFNγ and TNFα, ↓ mRNA expression of TIM-3 (splenocytes)	↓ Lesion size in established atheroscierotic plaques (thoraco-abdominal aorta and aortic root), ↓ CD4+ cells, ↓ macrophages, ↓ MMP-9, ↑ SMCs, ↑ collagen, ↓ mRNA of CCR2, CCR5 and CCL2/MCP-1	Male LDLR−/− mice	High chelesterol diet	Braunersreuther et al., 2008 [72]

Abbreviations: TC, total cholesterol; CA, carotid artery; TNF α, tumor necrosis factor alpha; LT-α, lymphotoxin alpha; Chimeric TNF-RI/Fc, recombinant murine TNF-RI fused with Fc fragment of human IgG; IL, interleukin; SMC, smooth muscle cells; IFN-γ, interferon gamma; MIF, migration inhibitory factor; αSMA,alpha smooth muscle actin; Mac-1, macrophage antigen 1; Mac-2, macrophage antigen 2; ICAM-1, Inter-Cellular Adhesion Molecule 1; MMP2, matrix metallopeptidase 2; CD40L, CD40 ligand; CXCR, CXC chemokine receptor; CCR, chemokine (C–C motif) receptor; MCP1, monocyte chemotactic protein-1(CCL2), Tim-3, Th1-specific cell surface transmembrane protein; RANTES(CCL5),chemokine (C–C motif) ligand 5; LDLR, low-density lipoprotein (LDL) receptor; ApoE, apolipoprotein E.