Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement

Abstract

SUMMARYSystemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-g (IFN-g ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-b 1, Tumour necrosis factor (TNF)-a , sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1 a and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNF a and MCP-1 but reduced amounts of g -IFN and MDC. IL6, IL10, IL18, MIP-1 a and TNF a measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-b 1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.

Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis

“…Analysis of median levels of individual cytokines confirmed previously published studies showing upregulation of IL-1b, IL-6, IL-8, IL-10, IL-12p40, IL-15, IL-17, TNF-RI, TNF-RII, MIP1a, MIP-1b, MCP-1, HGF and IP-10 in SSc patients [13][14][15][16][17][18][19][20][21][22][23] and upregulation of IL-8, TNF-RI, TNF-RII, IL-12p40, MIP-1a, MIP1b, MIG and IP-10 in sarcoidosis [24][25][26][27]. Novel findings, as far as we are aware, for other individual biomarkers included increased serum IFN-a, MIG, IP-10, DR5 and eotaxin levels in SSc patients and elevated serum levels of RANTES, DR5, EGF and HGF in sarcoidosis compared with healthy controls.…”

CSF-1–dependant donor-derived macrophages mediate chronic graft-versus-host disease

“…Monocyte chemoattractant protein 1 (MCP-1/CCL2), a multifunctional chemokine belonging to the C-C chemokine superfamily, has been shown to be upregulated in a variety of fibrotic conditions (25)(26)(27). Furthermore, patients with scleroderma exhibit elevated levels of CCL2 in both serum and skin (28,29). Similarly, we found elevated levels of CCL2 in the serum from 7 to 28 days after transplantation in lethally irradiated mice receiving BM plus T cell grafts (Allo) compared with levels detected in TCD non-GVHD controls ( Figure 8A).…”

An MIF Promoter Polymorphism Is Associated with Susceptibility to Pulmonary Arterial Hypertension in Diffuse Cutaneous Systemic Sclerosis

“…As a cytokine, MIF induces the expression and secretion of several immune mediators, including interleukin-6 (IL-6) [23]. Increased levels of IL-6 have been described in serum and lungs of idiopathic PAH patients and those with dcSSc compared to lcSSc [24,25], and IL-6 has a proved effect on the generation and development of PAH in vivo [24]. Moreover, allelic combinations of SNPs in the IL-6 gene have been suggested as susceptibility factors for SSc [26].…”