losartan-potassium and Lymphopenia

During the course of HIV disease a broad spectrum of hematologic disorders develop including abnormalities in blood cell generation, survival, and function Alterations in coagulation parameters may evolve associated with disruption of immunoglobulin or factor production. This article reviews the manifestations and pathophysiology of these abnormalities and discusses the role for growth factor support.

Topics: Blood Coagulation Disorders; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Hematologic Diseases; HIV Infections; Humans; Lymphopenia

Lymphocytopenia is associated with an adverse prognosis in heart failure (HF). The present study investigated whether lymphocytopenia results from activated lymphocyte autophagy/apoptosis, which reflects haemodynamic inefficiency and functional aerobic impairment in patients with HF. One hundred and twenty-seven patients with HF were divided into three groups: HF with non- (lymphocytes ≥2000 cells/μl; n=45), mild (lymphocytes between ≥1500 cells/μl and <2000 cells/μl; n=39) and severe (lymphocytes <1500 cells/μl; n=43) lymphocytopenia. Lymphocyte autophagy/apoptosis, ventilatory/haemodynamic efficiencies and generic/disease-specific quality of life were analysed in these patients with HF and 35 normal counterparts. The results demonstrated that patients with HF with severe lymphocytopenia had (i) increased G-protein-coupled receptor kinase-2 (GRK-2) levels, (ii) lower mammalian target of rapamycin (mTOR) levels with higher lysosome-associated membrane protein-2 (LAMP-2) expression and Acridine Orange (AO) staining, (iii) lower mitochondrial transmembrane potential with higher caspase-3 activation and phosphatidylserine (PS) exposure, and (iv) greater extents of adrenaline (epinephrine)-induced apoptosis in lymphocytes, and higher plasma noradrenaline (norepinephrine)/adrenaline, myeloperoxidase and interleukin-6 concentrations than patients with HF without lymphocytopenia and normal counterparts did. Moreover, lymphocyte caspase-3 activation was an effect modifier, which modulated the correlation status between lymphocyte count and GRK-2 level. Lymphocyte count was positively correlated with peak cardiac output and peak oxygen consumption (VO2peak) in patients with HF. In addition, HF with lymphocytopenia was accompanied by lower Short Form-36 physical/mental component scores and increased Minnesota Living with Heart Failure Questionnaire scores. Therefore, we conclude that increased sympathetic activation and oxidative stress/pro-inflammatory status cause lymphocytopenia by activating programmed lymphocyte death in patients with HF. Moreover, a low lymphocyte count correlates with reduced haemodynamics and aerobic capacity, which reflects poor generic/disease-specific quality of life in patients with HF.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Autophagy; Catecholamines; Cytokines; Erythropoietin; Female; G-Protein-Coupled Receptor Kinase 2; Heart Failure; Hemodynamics; Humans; Lymphocytes; Lymphopenia; Lysosomal-Associated Membrane Protein 2; Male; Membrane Potential, Mitochondrial; Middle Aged; Oxygen Consumption; Peroxides; Quality of Life; Regression Analysis; Surveys and Questionnaires; TOR Serine-Threonine Kinases

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.

Topics: Aged; Aged, 80 and over; Annexin A5; Apoptosis; Biomarkers; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cross-Sectional Studies; Erythropoietin; Female; Flow Cytometry; Humans; Kidney Failure, Chronic; Lymphopenia; Male; Middle Aged; Recombinant Proteins; Renal Dialysis