Table 2

Primary vascular sources, targets, and selected effects of interleukins for which a pro- or anti-atherogenic role has been established in murine intervention studies.

	Primary Sources	Primary Vascular Effector Cells and Direct Effects		Murine Intervention Studies
		Endothelial Cells			Monocytes/Macrophages		Smooth Muscle Cells
		⇑	⇓		⇑	⇓	⇑	⇓
IL-1	EC, T cell, MΦ, SMC (IL-1ra: EC, MΦ, SMC)	IL-1, IL-6, IL-8, MCP-1, M-CSF, fractalkine,	proliferation	IL-6	apolipoprotein E	IL-6, IL-8, IL-11, MCP-1, M-CSF,	proliferation	⇑ vascular inflammation in IL-1ra-deficient mice
		IL-1R1, ICAM-1, VCAM-1, E-selectin, tissue factor, heme oxygenase, apoptosis		PDGF-AA, superoxide		GM-CSF,ICAM-1, VCAM-1, iNOS, COX-2, Mn-SOD, stromelysin, interstitial collagenase, proliferation		⇓ atherogenesis in IL-1ra-transgenic mice

IL-6	EC, MΦ, SMC	IL-6, migration	HGF proliferation	MCP-1	SR-A	Proliferation		rIL-6 ⇓ fatty streak formation
								rIL-6 ⇑ atherogenesis
								rIL-6 ⇓ plaque progression
IL-8	EC, MΦ, SMC	Monocyte adhesion			TIMP-1	Chemotaxis, proliferation		⇑ atherogenesis following transfer of IL-8-transgenic bone marrow
IL-12	EC, MΦ	VCAM-1						rIL-12 ⇑ plaque progression
IL-9	T cell				TNFα oxidative burst			IL-9 ⇓ atherogenesis
								IL-9 immunization ⇑ atherogenesis
IL-10	T cell, MΦ		IL-6, IL-8	TIMP-1, differentiation, phagocytosis	Cytokine production, TNFα		PLA₂, proliferation	⇑ atherogenesis in IL-10-deficient mice
			VCAM-1, ICAM-1, P-selectin, E-selectin, angiogenesis		ICAM-1, CD18, CD62-L, tissue factor			⇓ atherogenesis in IL-10-transgenic mice
					iNOS			⇓ atherogenesis following transfer of IL-10-transgenic bone marrow
					MMP-9			plasmid-mediated/ adenoviral IL-10 gene transfer ⇓ atherogenesis
					MHC II, B7,
					NF-κB activation,
					activation,
					proliferation

Cox-2, cyclooxygenase-2; EC, endothelial cell; HGF, hepatic growth factor; M-CSF, monocyte colony-stimulating factor; PLA₂, phospholipase A₂; SR-A, scavenger receptor-A; TIMP-1, tissue inhibitor of metalloproteinase-1.