Table 2.

The mechanisms of different cytokines in AMD.

Cytokine	Research type	Mechanism(s)
IL-1	In vitro	IL-1α induces inflammasome which increases the sensitivity of RPE cell to cell death mediated by photooxidative damage and the mechanism of cell death becomes pyroptosis 55
	In vivo	IL-1Ra therapy signally suppresses CNV 56, 57
IL-2	In vitro	IL-2 contributes to cell migration, ECM synthesis and TGF-β2 expression via JAK/STAT3 and NF-κB signaling pathways 59
IL-4	In vivo + in vitro	lL-4 suppresses angiogenesis via Arg-1+ macrophage sFlt-1 80
IL-6	In vitro	Proteasome inhibitor MG132 upregulates IL-6 secretion by activating of P38 MAPKs 61
	In vivo + in vitro	IL-6, expressed by activated macrophages, promotes subretinal fibrosis 60 IL-6R-mediated activation of STAT3 contributes to CNV 62
IL-8	In vitro	Intracellular calcium mobilization promotes IL-8 secretion through NF-κB pathway 63 CRP can induce IL-8 expression by multiple pathways 64 25-OH causes IL-8 production through AP-1 and NF-κB pathways 65
IL-10	In vivo + in vitro	IL-10/STAT3 signaling contributes to pathological angiogenesis in senescent macrophages 81 IL-10(-/-) mice can reduce CNV with increased macrophage infiltrates 82 HSP70 induces IL-10 production through TLR2 and TLR4, and reduces subretinal fibrosis 84
	In vivo	CNV is inhibited by low-dose LPS pretreatment through IL-10 secretion by macrophages 83
IL-13	In vitro	IL-13 suppresses ARPE-19 cell proliferation and promotes fibrogenesis 85
IL-17	In vitro	IL-17 involves in choroidal angiogenesis via PI3K-Rac1 and RhoA-mediated actin cytoskeleton remodeling 76
	In vivo + in vitro	IL-17A causes the death of RPE cells by activating Casepase-9 and Casepase-3 77 and activates IL-1β production 78. IL-17 contributes to CNV, and IL-17 mainly produced by γδT cells not Th17 cells in the ocular lesions 75 IL-17 involves inflammation in CNV lesions, through producing γδT cells to strengthen the immune response and probably in a C5a-dependent manner 50.
IFN	In vitro	IFN-γ induces VEGF secretion by PI-3K/mTOR/translational pathway 73
	In vivo	IFN-β therapy weaken microgliosis and macrophage responses in the early AMD and decreased CNV size in the late AMD 71
TGF-β	In vivo	The inhibition of TGF-β/Smad signaling suppresses CNV via down-regulation of VEGF and TNF-α 88 Lack of TGF-β signaling promotes CNV 89, 90
TNF	In vivo +in vitro	BMP4 is down-regulated by TNF by activating JNK pathways in CNV 68 TNF-α promotes CNV by upregulating VEGF secretion via ROS-dependent activation of β-catenin signaling 66
	In vivo	Anti-TNF-α therapy reduces CNV 67