Interleukin-17 and Tumor Necrosis Factor Show a Functional Hierarchy to Regulate the Production of Matrix Metalloproteases by Monocytes from Patients with Psoriasis.

Abstract

Interleukin-17 (IL-17) and tumor necrosis factor (TNF) regulate tissue remodeling through matrix metalloproteinases (MMPs). It is not yet clear whether these cytokines have a functional hierarchy in psoriasis. Serum levels of TNF (1,403 versus 1,058 pg/mL), IL-17 (1,528 versus 820 pg/mL), MMP-1 (1,999 versus 1,039 pg/mL), and MMP-9 (1,950 versus 1,561 pg/mL) were higher in psoriasis subjects (n = 60) than in control subjects (n = 60). Tissue inhibitor of MMPs (TIMP-1; 1,374 versus 1,218 pg/mL) was lower in psoriasis subjects. Serum IL-17 was correlated with MMP-2 (rs = 0.40) and TIMP-1 (rs = -0.26) levels. Unstimulated production of MMP-1, MMP-2, and MMP-9 by monocytes was higher in psoriasis subjects, whereas TIMP-1 production was lower. TNF stimulation increased all MMPs, whereas TIMP-1 production was unchanged. IL-17 stimulation increased all MMPs, whereas TIMP-1 production was decreased in psoriasis subjects. MMP-9 production was higher in monocytes stimulated with IL-17 compared with TNF. TIMP-1 production was decreased more by IL-17 than by TNF, but only in psoriasis cells. MMP-1/TIMP-1, MMP-2/TIMP-1, and MMP-9/TIMP-1 ratios were higher after IL-17 stimulation (compared with TNF stimulation) in psoriasis subjects; this occurred in controls only for the MMP-2/TIMP-1 ratio. IL-17 has a greater ability than TNF to dysregulate the MMPs/TIMP-1 balance, supporting IL-17 blockade as first-line treatment in cutaneous psoriasis.