Table 1.

Proinflammatory cytokines involved in OA.

Cytokine	Expression	Functions	References
TNF-α	Synoviocytes Chondrocytes	Increase cartilage degradation and bone resorption	[80,81]
		Inhibit glycoprotein and collagen synthesis.	[82]
		Upregulate MMP expression	[83]
		Stimulate other cells to produce proinflammatory cytokines and growth factors	[84]
		Stimulate proangiogenic factor release	[85]
		Stimulate other cells to produce chemotactic cytokines	[86,87]
		Stimulate Nitric Oxide (NO) production	[88]
		Induce chondrocyte apoptosis	[89]
IL-1β	Synoviocytes Chondrocytes Macrophages	Increase cartilage degradation and bone resorption	[80,81,90]
		Inhibit proteoglycan synthesis	[91,92]
		Upregulate MMP expression	[93]
		Production of proteolytic enzymes	[94]
		Stimulate other cells to produce proinflammatory cytokines	[77]
		Stimulate other cells to produce chemotactic cytokines	[86,87]
		Stimulate proangiogenic factor release	[85]
		Stimulate NO production	[95]
		Induce chondrocyte apoptosis	[89]
IL-6	Synoviocytes Chondrocytes osteoblasts	Inhibit proteoglycan synthesis	[96]
		Reduce chondrocyte proliferation	[96]
		Increase MMP-2 activity	[97]
		Increase aggrecanase-mediated proteoglycan catabolism	[98]
IL-8	Monocytes Synoviocytes Chondrocytes Osteoblasts	Recruits leucocytes	[99]
		Neutrophil chemoattractant	[100]
		Stimulates release of proinflammatory cytokines	[101]
		Hypertrophic differentiation and calcification of chondrocytes	[102]
IL-17	Activated T-lymphocytes	Induce NO synthesis	[103,104]
		Induce MMP synthesis	[103,104]
		Increase production of IL-1β, Il-6 and IL-8	[103,105]
		Stimulate release of proangiogenic factors	[106]
IL-18	Macrophages Synovial fibroblasts	Stimulate release of proinflammatory cytokines	[107,108]
		Stimulate angiogenesis	[109]
		Induce NO synthesis	[108]
		Synovial hyperplasia and inflammatory cell recruitment	[110]
		Induce chondrocyte apoptosis	[111]
		Reduce expression of cartilage matrix components	[111]
		Up-regulate fibronectin- a mediator of cartilage destruction	[111]
Leukaemia Inhibitory Factor (LIF)	Synovial fibroblasts Chondrocytes	Stimulate proinflammatory cytokine expression	[112,113]
		Increase pro-MMP-2 synthesis	[97]
		Increase MMP-13 synthesis and activity	[114]
		Increase cartilage resorption	[115]
		Decrease proteoglycan synthesis	[116]
		Leukocyte infiltration into synovial fluid	[117]
		Increase cartilage degradation when in combination with IL-1β and TNF-α	[115]