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

The utility of cytokine monitoring to predict the onset of significant rejection was evaluated in 34 patients following heart transplantatio n. Serial blood levels of 5 cytokines involved in inflammation and imm une activation(IL-1, IL-2, IL-6, IL-8, and TNF) were correlated with c linical outcome and endomyocardial biopsy scores. The majority of pati ents(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 10 00 pg/ml predicted the onset of rejection with sensitivities of 75% an d 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-fre e course with sensitivities of 91% and 91% and specificities of 81% an d 68%, respectively. The remaining cytokines differentiated patients e xperiencing a clinically unremarkable course from those experiencing m ild-to-moderate rejection but did not discriminate rejection severity. IL-6 levels identified steroid and OKT3 resistance within 48 hr of an tirejection therapy. IL-6 levels elevated to 197 +/- 20 pg/ml among st eroid-resistant patients and normalized to 20 a 5 pg/ml among responde rs. 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 u seful markers of rejection and therapeutic efficacy following heart tr ansplantation.