THE PARADOX OF CYTOKINE MONITORING-PREDICTOR OF IMMUNOLOGIC ACTIVITY AS WELL AS IMMUNOLOGIC SILENCE FOLLOWING CARDIAC TRANSPLANTATION

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Abstract
The utility of cytokine monitoring to predict the onset of significant rejection was evaluated in 34 patients following heart transplantation. Serial blood levels of 5 cytokines involved in inflammation and immune activation(IL-1, IL-2, IL-6, IL-8, and TNF) were correlated with clinical outcome and endomyocardial biopsy scores. The majority of patients(68%) experienced a significant rejection during the study period. IL-6 and IL-8 levels were effective markers of significant rejection 2-4 days before diagnosis with EMBX. IL-6 and IL-8 levels of 15 and 1000 pg/ml predicted the onset of rejection with sensitivities of 75% and 66% and specificities of 86% and 76%, respectively. In contrast, IL-6 and IL-8 levels less than 15 and 400 pg/ml predicted a rejection-free course with sensitivities of 91% and 91% and specificities of 81% and 68%, respectively. The remaining cytokines differentiated patients experiencing a clinically unremarkable course from those experiencing mild-to-moderate rejection but did not discriminate rejection severity. IL-6 levels identified steroid and OKT3 resistance within 48 hr of antirejection therapy. IL-6 levels elevated to 197 ± 20 pg/ml among steroid-resistant patients and normalized to 20 ± 5 pg/ml among responders. IL-8 levels delineated OKT3 resistance. IL-8 levels rose to 3496 ± 500 pg/ml among nonresponders, whereas levels fell to 152 ± 50 pg/ml among responders. This study demonstrates that IL-6 and IL-8 are useful markers of rejection and therapeutic efficacy following heart transplantation