Abstract
Background: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. Methods: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1β, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-β) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. Results: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-β, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.
Highlights
IntroductionMany studies have reported increased levels of profibrotic T-helper (Th)-17 cells and Th-17 related cytokines in serum and skin [5,6] of Systemic sclerosis (SSc) patients
Systemic sclerosis (SSc) is a chronic connective tissue disorder, in which humoral and cellular immunity alterations lead to massive fibrosis of the skin and internal organs [1,2].Gastrointestinal involvement in systemic sclerosis is very common, affecting up to 87% of patients [3], with the esophagus being the most commonly involved tract, followed by rectum and small bowel [4].Many studies have reported increased levels of profibrotic T-helper (Th)-17 cells and Th-17 related cytokines in serum and skin [5,6] of SSc patients
According to the pattern of cutaneous involvement, 17 patients were diagnosed with limited SSc and 12 patients received the diagnosis of diffuse SSc
Summary
Many studies have reported increased levels of profibrotic T-helper (Th)-17 cells and Th-17 related cytokines in serum and skin [5,6] of SSc patients. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis
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