Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-κB ligand, and matrix metalloproteinases and drives bone and cartilage pathology in experimental arthritis: rationale for combination therapy in rheumatoid arthritis

Table 1 Quantitative PCR of synovial tissue after 2 weeks of antibody treatment during collagen-induced arthritis (fold increase over isotype control-treated samples (2^−ΔΔCt)

		Gene	Anti-IL-17	Anti-GM-CSF	Anti-IL-17 + anti-GM-CSF
Damaging	Proinflammatory T cell factors	IL-17A	1.63 ± 0.56	not detected	1.48 ± 1.0
		GM-CSF	1.12 ± 0.73	0.55 ± 0.54	0.55 ± 0.2
		RORγt	5.06 ± 2.94^a,b	0.68 ± 0.30^c	1.68 ± 0.96^c
		IL-21	2.30 ± 1.14	0.88 ± 0.61	0.71 ± 0.35
		RANKL	0.97 ± 0.49	0.36 ± 0.19	0.80 ± 0.56
	Matrix metalloproteinases	MMP3	0.87 ± 0.45	0.24 ± 0.10	0.51 ± 0.26
		MMP9	1.18 ± 0.71	0.36 ± 0.18	0.75 ± 0.42
		MMP13	0.89 ± 0.38	0.44 ± 0.18	0.60 ± 0.31
		MMP14	1.43 ± 0.55	0.58 ± 0.22	0.74 ± 0.32
		ADAMTS5	1.34 ± 0.67	0.43 ± 0.24	0.89 ± 0.50
	Alarmin	S100A8	1.82 ± 0.93	0.56 ± 0.23	1.08 ± 0.58
	Pro-inflammatory DC/Mϕ-derived	IL-1β	1.09 ± 0.44	0.85 ± 0.40	1.67 ± 1.03
	Pro-inflammatory DC/Mϕ-derived	IL-23	0.45 ± 0.19	1.02 ± 0.56	1.71 ± 0.89
Protective	Anti-inflammatory T cell factor	IL-10	1.53 ± 0.81	0.62 ± 0.38	0.71 ± 0.35
	Matrix metalloproteinase inhibitors	TIMP1	1.31 ± 0.56	0.48 ± 0.23	0.85 ± 0.42
		TIMP2	1.05 ± 0.39	0.50 ± 0.18	0.58 ± 0.25
		TIMP3	0.77 ± 0.09	0.63 ± 0.15	0.70 ± 0.09
		TIMP4	0.79 ± 0.19	0.97 ± 0.19	0.91 ± 0.22
	Th1/Th2 transcription factors	T-bet	1.75 ± 0.53	0.77 ± 0.11	0.84 ± 0.18
	Th1/Th2 transcription factors	GATA3	1.87 ± 0.71	0.67 ± 0.27	0.69 ± 0.20

GM-CSF granulocyte macrophage colony-stimulating factor, IL interleukin, Th helper T cell
n = 6 mice/treatment group
^a p ≤ 0.001 vs. anti-IL-17 + anti-GM-CSF (two-way analysis of variance and Bonferroni’s multiple-comparisons test)
^b p ≤ 0.0001 vs. anti-GM-CSF
^c p ≤ 0.0001 vs. anti-IL-17

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