Table 1.

Rationale for IL-6 blockade in SLE

Murine models of SLE	Age related increase in serum IL-6 and soluble IL-6R levels
	Abnormal expression of IL-6R
	IL-6 increases autoantibody production
	Blocking IL-6 decreases autoantibody production
	Anti-dsDNA antibody production was blocked in IL6 ‐ /‐ mice
	Exogenous IL-6 accelerated the progression of glomerulonephritis
	Blocking IL6
	prevented age related increases in anti-dsDNA levels
	progression of proteinuria
	improved survival
IL-6 in human SLE Systemic	Increased serum IL-6 levels in active lupus
	Higher frequency of IL-6 secreting PBMCs
	Increased IL-6 production by T and B cells
	Increased expression of IL-6R on low density B cells in active lupus
	Blocking IL-6 decreased spontaneous Ig and dsDNA production ex vivo
	Effect on regulatory T cells unclear – may be different on various subsets
	Anti-dsDNA antibodies upregulate IL-6 production by endothelial cells and resting mononuclear cells and in turn IL-6 increases the production of dsDNA antibodies
Effects on kidney	IL-6 increases mesangial cell proliferation
	Important in related immune mediated glomerulonephritides
	Increased IL-6 expression in the kidneys in lupus nephritis
	Increased urinary IL-6 levels during active lupus nephritis