IL-33/ST2 pathway and classical cytokines in end-stage heart failure patients submitted to left ventricular assist device support: a paradoxic role for inflammatory mediators?

BACKGROUND: Inflammation is a critical process contributing to heart failure (HF). We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. METHODS: IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post-LVAD). RESULTS: Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVAD than in the HT group. LVAD determined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. CONCLUSIONS: IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course. Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies.

"Popular" health and the state: dialectics of the peace process in El Salvador.

The poor performance of large-scale "vertical" rural health programs tied to state Ministries of Health in Third World countries has often been attributed to a lack of "political will". But that term tells little about the conditions that favor health reform and may obscure disparate power relations and struggles over development. This work explores such a struggle over community health that emerged as part of the peace process in a former war zone of El Salvador since the 1992 ceasefire. The formalized negotiations (and behind-the-scenes confrontations) over health in Chalatenango province took place between Ministry of Health administrators and proponents of a "popular" health system that has functioned in repopulated villages of rebel-controlled Chalatenango since 1987. The Ministry has set up its own national (U.S. AID-designed) community health worker program, and agreed in theory with the popular system's emphasis on village-based lay health promoters; however, in negotiations and efforts at collaboration in Chalatenango the Ministry has been unwilling to support the promoters in the popular system, to accommodate local participation in health decision-making, or to restructure its own physician-centered practices around the need for more comprehensive approaches to health.