Circulating cytokine portraits can differentiate between allograft rejection and pulmonary infection in cardiac transplant rats

Abstract

Objectives: Cardiac rejection and infection are the leading causes of morbidity and mortality after transplant representing with similar non-specific symptoms. Early discrimination is crucial yet challenging. We proposed that aberrant serum cytokine portraits exist in pulmonary infection and allograft rejection, and such profiles might aid in timely differential diagnosis.

Methods: Lewis rat received Wistar rat heart allografts. Allograft rejection (n = 5) and pulmonary infection (n = 7) were induced via cessation of cyclosporine injection and intratracheal inoculation of Pseudomonas aeruginosa, respectively, and pathologically confirmed. A non-rejection and non-infection group (n = 5) was served as healthy controls. The circulating cytokine profiles of the study objects were then simultaneously measured using a multiplex quantitative cytokine array.

Results: Thirteen cytokines [B7-2, β-nerve growth factor (NGF), chemokine (C-X3-C motif) ligand 1 (Fractalkine), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interleukin beta (IL-β), IL-2, IL-4, IL-10, chemokine (C-X-C motif) ligand 5 (LIX), L-selectin, chemokine (C-C motif) ligand 2 (MCP-1), brain creatine kinase (TCK-1) and tumour necrosis factor alpha (TNF-α)] were up-regulated in allograft rejecting animals. Among them, B7-2, β-NGF, Fractalkine, GM-CSF, IFN-γ, IL-β, IL-2, IL-4, LIX, MCP-1 and TCK-1 were significantly increased compared with infection rats (all P-values <0.05). B7-2, CNIC-1 and CNIC-2 were increased in infection animals when compared with healthy controls (900.85 ± 259.30 vs 175.04 ± 161.07 pg/ml, 319.68 ± 264.91 vs 13.50 ± 0.00 pg/ml and 51.424 ± 29.51 vs 5.24 ± 1.30 pg/ml, respectively, all P-values <0.05).

Conclusions: The present study demonstrated fluctuations in circulating cytokine portraits in cardiac allograft rejection and bacterial pulmonary infection after transplant. Such disease-specific cytokine patterns might facilitate early discrimination between rejection and infection.

Keywords: Cytokine profile; Differential diagnosis; Heart transplant; Infection; Rat; Rejection.