The regulatory activity of interleukin-35 on CD14+monocytes in patients with chronic heart failure

Abstract

Objective: To investigate the changes of interleukin-35 (IL-35) level and CD14+monocytes function in patients with chronic heart failure (CHF). Methods: A total of 74 patients with CHF who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Zhengzhou University between July 2018 and June 2019 as well as 29 healthy controls (HC) were continuously enrolled. 20 ml fasting anticoagulant peripheral blood was collected in the morning, and plasma was separated. IL-35 level was measured by ELISA. Peripheral CD14+monocytes were purified, and the IL-35 receptor subunits (IL-12Rβ2 and gp130 mRNA) relative levels were semi-quantified by real-time PCR. CD14+monocytes were stimulated with IL-35, and were cultured in direct contact or indirect contact with human umbilical vein endothelial cells (HUVEC). Cytokines and granzyme B secretion in the supernatants was measured by ELISA. The percentage of HUVEC death was calculated by measuring lactate dehydrogenase level. The difference of the above indicators were compared between the CHF group and the HC group. Results: The age for the CHF group was (59.4±12.1) years, and 58.1% (43 cases) of them were males. The age for the HC group was (53.9±9.8) years, and 65.5% (19 cases) of them were males. The plasma IL-35 level was higher in the CHF group than the HC group ((22.89±7.58) mg/L vs (16.42±5.47) mg/L, P<0.001). The gp130 mRNA relative level was also higher in the CHF group than the HC group (1.07±0.19 vs 0.98±0.15, P=0.022). CD14+monocytes induced HUVEC death in the CHF group was lower in both direct contact and indirect contact culture system than the HC group (both P<0.001). The granzyme B secretion was also lower in the CHF group than the HC group (P<0.001). The CD14+monocytes induced HUVEC death was down-regulated in response to granzyme B inhibition (P=0.011). Both the CD14+monocytes induced HUVEC death and the granzyme B secretion were reduced in response to IL-35 stimulation (both P<0.001). Conclusion: CHF patients have the elevated IL-35 expression. IL-35 induces CD14+monocytes dysfunction via the inhibition of granzyme B secretion. This process promoted the progression of heart failure.