The heart is a source of circulating cardiotrophin-1 in humans

Cardiotrophin-1 (CT-1) is a new member of the interleukin (IL)-6 family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, which has potent hypertrophic and survival effects on cardiac m yocytes. However, the clinical significance of CT-1 is poorly understood, m ainly because there is no widely applicable specific and sensitive assay sy stem for measuring plasma levels of circulating CT-1. We therefore develope d a competitive radioimmunoassay (RIA) for human CT-1 with rabbit antiserum recognizing the N-terminus region of human CT-1 and using recombinant huma n CT-1 as a calibrator. The assay displays no cross-reactivities with any o f the IL-6 family of cytokines including IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. The lower detection limit i n buffer was found to be 43 fmol/ml, and the working range was 120-8300 fmo l/ml (CV < 15%). This RIA directly recognizes CT-1-like immunoreactivity in human plasma with a mean value of 571 <plus/minus> 75 fmol/ml (mean +/- SD ) in healthy volunteers. The RIA coupled with gel filtration chromatographi c analyses showed that the major molecular form of circulating CT-1 corresp onds to recombinant full-length human CT-1. Moreover, there is a significan t increase in the plasma CT-1 concentration from the aorta and coronary sin us, which clearly indicates that the heart secretes CT-1 via the coronary s inus into the peripheral circulation. This RIA should serve as a powerful t ool for investigating the clinical significance of CT-1. (C) 2000 Academic Press.