Rapid alteration of serum interleukin‐6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis‐associated interstitial lung disease

Abstract

Systemic sclerosis (SSc) is an autoimmune disorder characterized by excessive extracellular matrix deposition. Although SSc-associated interstitial lung disease (ILD) is one of the most important complications as a cause of death in SSc, prediction factors of treatment reactivity in SSc-ILD are still unclear. To assess relationships between interleukin (IL)-6 and reactivity to treatment, we measured serum IL-6 levels in 23 of active SSc-ILD patients under i.v. cyclophosphamide (IVCY) therapy and 20 of stabilized SSc-ILD, using the high-sensitivity enzyme-linked immunoassay system. Serum IL-6 levels in active SSc-ILD patients were significantly higher than those in stabilized SSc-ILD patients. Among active SSc-ILD patients, baseline serum IL-6 levels were not significantly different between IVCY responders and non-responders. Meanwhile, serum IL-6 levels after three IVCY doses out of a total of six were decreased in responders but not in non-responders. Regarding changes of parameters by the three doses of a total of six of IVCY, change in serum IL-6 levels correlated inversely with that in values of pulmonary function test. Thus, the rapid decrease in serum IL-6 levels during a couple of doses may predict the efficacy of IVCY therapy against SSc-ILD.

Screening and identification of potential biomarkers and therapeutic targets for systemic sclerosis-associated interstitial lung disease

“…[ 17 ] Serum IL-6 levels can be also used as an evaluation index for the efficacy of cyclophosphamide in the treatment of SSc-ILD. [ 18 ] Studies have confirmed that IL-6 is involved in the pathogenesis of SSc. [ 19 ] Interleukin 6 is implicated in the process of pulmonary fibrosis by promoting the upregulation of collagen-related gene expression, promoting the proliferation and differentiation of fibroblasts and myofibroblasts, inhibiting T cell apoptosis, and regulating the balance of Th17 cells and Treg cells.…”

Role of B-Cell in the Pathogenesis of Systemic Sclerosis

“…There is, therefore, a loop between the fibroblast and the B-cell that is partly dependent on IL-6. Noteworthy, IL-6 and IL-10 serum levels correlated with skin and pulmonary fibrosis ( 82 , 83 ). Otherwise, circulating B-cells secrete increased amounts of IL-8, IL-1β, BAFF, and CXCL13, which are proinflammatory, profibrotic cytokines or chemo-attractant molecules, both in scleroderma mouse models and SSc patients ( 20 , 22 , 37 , 84 ).…”

Peripheral blood IL‐6 levels in systemic sclerosis patients: Correlation between IL‐6 levels and clinical phenotypes

“…29 The results of previous studies have shown that the level of IL-6 in the serum of SSc patients is higher than that of the healthy control group, and it may be related to the activity state, severity, and prognosis of the disease. 30,31 The correlation between IL-6 and clinical phenotypes can be affected by the course of the disease, sample size, and testing methods. Hasegawaet al found that serum IL-6 levels in patients with SSc fibrosis were lower than those in non-fibrotic patients.…”