Serological cytokine profiles of cardiac rejection and lung infection after heart transplantation in rats

Hao Chen,Xuan Qin,Shengchao Zhang,Juhua Yang,Feng Li,Wei Jin,Lihua Sun,Yunfeng Cheng

doi:10.1186/s13019-019-0839-5

Abstract

BackgroundAllograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Early differential diagnosis is clinically crucial but difficult. The aim of the study was to examine serum cytokine profiles associated with each entity and whether such profiles could help to differentiate between them.MethodsHeart allografts from Wistar rats were transplanted to Lewis rats as described by Yokoyama. Cardiac rejection and pulmonary bacterial infection were induced by Cyclosporine cessation and bacteria bronchus injection, and pathologically confirmed. Ninety serological cytokines profiles of the study objects were then simultaneously measured using a biotin label-based cytokine array. The fold change (FC) was used for relative cytokine concentration comparison analysis.ResultsFour cytokines in cardiac rejection group were significantly dysregulated as compared to health controls (β -Catenin, 0.51 FC; E-Selectin, 0.62 FC; IFN-gamma, 1.87 FC; and IL-13, 0.60 FC, respectively). In pulmonary infection animals, 11 cytokines were remarkably dysregulated in comparison with the control group (CINC-3, 0.57 FC; CNTF R alpha, 0.59 FC; E-Selectin, 0.58 FC; FSL1,0.62 FC; Hepassocin, 0.64 FC; IL-2, 0.26 FC; IL-13, 0.49 FC; NGFR, 0.57 FC; RAGE, 0.50 FC; TIMP-1, 0.49 FC; and IFN-gamma, 1.77 FC, respectively). Eleven cytokines were significantly up-regulated in cardiac rejection group comparing to the pulmonary infection animals (FSL1, 2.32FC; Fractalkine, 1.65FC; GFR alpha-1, 1.64FC; IL-2, 2.72FC; IL-5, 1.60FC; MMP-2, 1.71FC; NGFR, 2.25FC; TGF-beta1, 1.58FC; TGF-beta3, 1.58FC; Thrombospondin, 1.64FC, and TIMP-1, 1.52FC, respectively).ConclusionsThe current study illustrated the disease-specific serological cytokine profiles of allograft rejection and pulmonary bacterial infection after cardiac transplant. Such disease associated cytokine portraits might have the potential for early discrimination diagnosis.

Highlights

Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant
Heterotopic cardiac transplantation Cardiac allograft rejection and pulmonary bacterial infection were induced as the following [4]
The allograft heartbeat of the non-rejection animals remained energetic throughout the study period, while the transplanted heart gradually lost its contractions over time after cyclosporine A (CSA) cessation in the rejection group

Summary

Introduction

Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Acute cardiac allograft rejection and infection are the major causes of death for cardiac transplanted patients, accounting for almost 40% reported deaths within the first year after the surgery [1]. Chen et al Journal of Cardiothoracic Surgery (2019) 14:26 underlying mechanisms of cardiac rejection and infection that complicating heart transplant. Using an animal model of lung bacterial infection after heterotopic cardiac transplantation we have recently developed [4], the current study simultaneously examined ninety serological cytokines profiles in the course of acute cardiac rejection and pulmonary infection with a biotin-labeled-based cytokine protein array system. Our hypotheses are 1) disease-specific cytokine pattern exists in each entity, and 2) such cytokine patterns might have the potential to aid differential diagnosis

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Conclusion