Soluble cytokine receptors in idiopathic pulmonary fibrosis

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Background: The clinical prevalence of circulating soluble cytokine receptors has been undetermined in idiopathic pulmonary fibrosis (IPF), whereas comprehensive evaluation of circulating cytokines identified a candidate for blood biomarker. Aims and objectives: To evaluate circulating soluble cytokine receptors as blood biomarkers for IPF. Methods: Fourteen soluble cytokine receptors (sCD3, sEGFR, sgp130, sIL-1RI, sIL1-RII, sIL-2Ra, sIL-4R, sIL-6R, sRAGE, sTNFRI, sTNFRII, sVEGFR1, sVEGFR2 and sVEGFR3) were measured in the sera of patients with IPF from two independent cohorts (cohort 1, n=98; cohort 2, n=110) and healthy individuals (n=28), and were compared between patients with IPF and controls. The associations of soluble cytokine receptor with pulmonary functions and outcomes were analyzed in the two IPF cohorts. Results: Serum sIL-2Ra, sIL-4R, sTNFRI, and sTNFRII were elevated in both cohorts of IPF, compared to healthy individuals: sIL-2Ra: cohort 1, 470.6 ng/mL, cohort 2, 538.6 ng/mL, control, 281.0 ng/mL; sIL-4R: cohort 1, 213.2 ng/mL, cohort 2, 142.7 ng/mL, control, 0.0 ng/mL; sTNFRI: cohort 1, 691.0 ng/mL, cohort 2, 751.1 ng/mL, control, 422.8 ng/mL, and sTNFRII: cohort 1, 4441.9 ng/mL, cohort 2, 4541.6 ng/mL, control, 3216.6 ng/mL. There was no association between any of these four soluble cytokine receptors (sIL-2Ra, sIL-4R, sTNFRI, and sTNFRII) and pulmonary functions in either of two cohorts. None of these four soluble cytokine receptors was predictive for one-year progression or overall survival in either of two cohorts. Conclusions: Some of serum soluble cytokine receptors were elevated in IPF, though the potential roles of soluble cytokine receptors may be limited as blood biomarkers for IPF.

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