SPONTANEOUS ENDOTHELIN PRODUCTION BY CIRCULATING MONONUCLEAR-CELLS FROM PATIENTS WITH CHRONIC HEART-FAILURE BUT NOT FROM NORMAL SUBJECTS

1. Plasma endothelin-1 (ET-1) levels are increased in chronic heart failure (CHF). Because chronic immunologic activation occurs in CHF and mononuclear cells (MNC) are capable of ET-1 production, the possible contribution of circulating MNC to the increased plasma ET-1 levels in CHF patients was investigated. 2. Unseparated MNC (10(7)/mL) from eight CHF patients spontaneously produced ET-1 (1.54 +/- 0.37 pg/100 mL). After separation of MNC into monocytes (10(6)/mL) and lymphocytes (10(7)/mL) at ratios approximating those in the circulation, ET-1 was spontaneously produced by CHF lymphocytes (0.81 +/- 0.26 pg/100 mL), and after macrophage colony stimulating factor (MCSF) stimulation by CHF monocytes (0.56 +/- 0.08 pg/100 mL). In contrast, there was neither spontaneous nor MCSF-induced production of ET-1 in six normal subjects. 3. It was concluded that heightened ET-1 production by MNC may contribute to increased plasma levels in CHF patients. Because unseparated MNC produced greater ET-1 than lymphocytes and monocytes separately, contact between these MNC subtypes may be necessary for maximal ET-1 production.