2026-04-17T01:38:39Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2129152025-12-04T21:26:36Zcom_2072_1057col_2072_478779col_2072_478917

00925njm 22002777a 4500 dc del Fresno, Carlos author Soler-Rangel, Llanos author Soares-Schanoski, Alessandra author Gómez-Piña, Vanesa author González-León, María Carmen author Gómez-García, Lourdes author Mendonza Barberá, Elena de author Rodríguez-Rojas, Alexandro author García, Felipe author Fuentes Prior, Pablo author Arnalich, Francisco author López Collazo, Eduardo author 2024-06-13T09:04:15Z 2024-06-13T09:04:15Z 2007-02-01 2024-06-13T09:04:21Z Acute coronary syndrome (ACS) groups different cardiac diseases whose development is associated with inflammation. Here we have analyzed the levels of inflammatory cytokines and of members of the TLR/IRAK pathway including IRAK-M in monocytes from ACS patients classified as either UA (unstable angina), STEMI (ST-elevation myocardial infarction) or NSTEMI (non-ST-elevation myocardial infarction). Circulating monocytes from all patients, but not from healthy individuals, showed high levels of pro-inflammatory cytokines, TNF-α and IL-6, as well as of IRAK-M and IL-10. TLR4 was also up-regulated, but IRAK-1, IRAK-4 and MyD88 levels were similar in patients and controls. Further, we investigated the consequences of cytokines/IRAK-M expression on the innate immune response to endotoxin. Ex vivo responses to LPS were markedly attenuated in patient monocytes compared to controls. Control monocytes cultured for 6 h in supplemented medium (10% serum from ACS patients) expressed IRAK-M, and LPS stimulation failed to induce TNF-α and IL-6 in these cultures. Pre-incubation of the serum with a blocking anti-TNF-α antibody reduced this endotoxin tolerance effect, suggesting that TNF-α controls this phenomenon, at least partially. We show for the first time that inflammatory responses associated with ACS induce an unresponsiveness state to endotoxin challenge in circulating monocytes, which correlates with expression of IRAK-M, TLR4 and IL-10. The magnitude of this response varies according to the clinical condition (UA, STEMI or NSTEMI), and is regulated by TNF-α. Inflamació Malalties cardiovasculars Inflammation Cardiovascular diseases Inflammatory responses associated with acute coronary syndrome up-regulate IRAK-M and induce endotoxin tolerance in circulating monocytes