Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner

Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF–primed monocyte–derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate–induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.This work was supported in part by grants from the Spanish Ministry of Science, Innovation and Universities (SAF2017-82940-R Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional (AEI/FEDER), Unión Europea [UE] [to M.M.], SAF2017-83785-R AEI/FEDER, UE [to Á.L.C.] and FJCI-2016-29990 AEI/FEDER, UE [to B.S.P.]), from the Redes Temáticas de Investigación Cooperativa en Salud Program of Instituto de Salud Carlos III (RD12/0012/0006 and RD12/0012/0007, Red de Investigación en Inflamación y Enfermedades Reumáticas), and the Regional Government of Madrid (B2017/BMD-3804 [to C.M.-A.])

Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control and family study

BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. Genetic and environmental factors are suspected to be involved in the development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory activity on immunoglobulin production and it may be an important regulator in IgAD pathogenesis. The IL-10 gene contains several single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers are associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278 patients with IgAD and 573 ethnically matched controls for the microsatellites IL-10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, -819 and -592 in the proximal promoter of the gene. We also included in this study the parents of 194 patients in order to study the IL-10 haplotypes transmitted and not transmitted to the affected offspring. RESULTS: The only allele where a significant difference was observed in the comparison between IgA deficiency patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However, this p value could not withstand a Bonferroni correction. None of the IL-10R or promoter SNP alleles was found at a different frequency when patients were compared with controls. CONCLUSION: Our data do not show any significant difference in IL-10 polymorphism frequencies between control and IgAD patient samples. Their haplotype distribution among patients and controls was also equivalent and therefore these microsatellites and SNPs do not seem to influence IgAD susceptibility

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Long-term outcomes among a nationwide cohort of patients using an implantable cardioverter-defibrillator : UMBRELLA study final results

Altres ajuts: Medtronic Iberica.BACKGROUND: Large-scale studies describing modern populations using an implantable cardioverter-defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real-world ICD patients with different heart disorders. METHODS AND RESULTS: The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29-1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07-1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43-2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54-0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14-0.45) showed a lower risk. All-cause death was 13.4% at follow-up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58-5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18-5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25-6.99) had the worst prognoses. Delayed high-rate detection was enabled in 39.7% of patients, and single-zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow-up was low (6%) and did not differ among type of ICD but was lower in SmartShock-capable devices. CONCLUSIONS: Irrespective of the cause, contemporary ICD patients with heart failure-related disorders had a similar risk of ICD life-saving interventions and death. Current ICD programming recommendations still need to be implemented