title: The paradox of cytokine monitoring-predictor of immunologic activity as well as immunologic silence following cardiac transplantation.
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 transplation.
authors.affiliation: Department of Surgery, Medical College of Virginia, Richmond 23298-0005, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Kimball
authors.forename: B
authors.initials: B
authors.lastname: Radovancĕvíc
authors.forename: T
authors.initials: T
authors.lastname: Isom
authors.forename: A
authors.initials: A
authors.lastname: Spickard
authors.forename: O H
authors.initials: OH
authors.lastname: Frazier
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016207:Cytokines / Q000097:blood*; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D015166:Monitoring, Immunologic; D016853:Muromonab-CD3 / Q000627:therapeutic use; D009206:Myocardium / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016853:Muromonab-CD3