Evaluation of plasma levels of tumour necrosis factor alpha and interleukin-6 as rejection markers in a cohort of 142 heart-grafted patients followed by endomyocardial biopsy

The rejection reaction after cell or organ transplantation has to be detected as early as possible in order to conduct optimal immunosuppressive treatment. Among the numerous events leading to rejection, cytokine production, especially of tumour necrosis factor alpha, is particularly important. Interleukin-6 and tumour necrosis factor alpha were investigated in 142 heart-grafted patients in order to define an early peripheral non-invasive marker of an acute rejection that could fit well with myocardial biopsy results. Cytokines were immunoenzymatically measured in blood specimens collected on the day of the endomyocardial biopsy. The values were compared to the grade of heart graft rejection established according to pathological criteria. Plasma interleukin-6 and especially tumour necrosis factor alpha determined on the day of the rejection diagnosis were significantly increased in the patient sample with moderate or severe rejection when compared with mean values of interleukin-6 and tumour necrosis factor alpha in the patient sample without rejection or with mild rejection (P=0·04 and 0·001 respectively). Because high levels of tumour necrosis factor alpha may appear before histological signs, this biological marker could be useful in the follow-up of heart-grafted patients.