Role of Cytokines in the Pathogenesis of Anemia of Chronic Disease in Rheumatoid Arthritis
ABSTRACT The aim of our study was to evaluate the role of proinflammatory cytokines: tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as the possible contribution of interleukin-10 (IL-10) in anemia of chronic disease (ACD) of rheumatoid arthritis (RA) patients. We measured the serum levels of TNFα, IL-1β, and IL-6 in 105 anemic and 127 nonanemic RA patients. We also investigated the effects of the above cytokines on the development of burst-forming units–erythroid (BFUe) and colony-forming units–erythroid (CFUe) in bone marrow cultures. Anemic patients had significantly higher serum levels of TNFα, IL-1β, and IL-6 compared to nonanemics. Serum IL-10 levels were low and there was no significant difference in IL-10 concentrations between anemic and nonanemic patients. Proinflammatory cytokines inhibited proliferation of BFUe and CFUe. IL-10 did not decrease the erythroid colony growth. Proinflammatory cytokines may play a role in the pathogenesis of ACD in RA patients. Low levels of IL-10 possibly contribute to the development of ACD.
- SourceAvailable from: Kazuko Uno[Show abstract] [Hide abstract]
ABSTRACT: Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients. Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR. Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab. Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production.Arthritis research & therapy 01/2013; 15(5):R141. · 4.12 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Objective. Pyelonephritis is a common infectious morbidity of pregnancy. Though anemia is commonly associated with pyelonephritis, there are little data describing the effect of pyelonephritis with anemia on pregnancy outcomes. The purpose of this study was to further assess the association of anemia with infectious morbidity and pregnancy complications among women with pyelonephritis. Study Design. We conducted a retrospective cohort study of pregnant women admitted to Duke University Hospital between July 2006 and May 2012 with pyelonephritis. Demographic, laboratory, and clinical data from the subject's pregnancy and hospitalizations were analyzed. Patients with pyelonephritis and anemia (a hematocrit < 32) were compared to those without anemia. Descriptive statistics were used to compare the two groups. Results. 114 pregnant women were admitted with pyelonephritis and 45 (39.5%) had anemia on admission. There was no significant difference in age, race, preexisting medical conditions, or urine bacterial species between patients with anemia and those without. Women with anemia were more likely to deliver preterm (OR 3.3 (95% CI 1.07, 11.4), P = 0.04). When controlling for race and history of preterm delivery, women with anemia continued to have increased odds of preterm birth (OR 6.0, CI 1.4, 35, P = 0.012). Conclusion. Women with pyelonephritis and anemia are at increased risk for preterm delivery.Infectious Diseases in Obstetrics and Gynecology 01/2013; 2013:780960.
- [Show abstract] [Hide abstract]
ABSTRACT: The treatment of the infection is still challenging in children with severe malnutrition and immunosupression. Objective: evaluate and compare inflammatory markers such as C–reactive protein (CRP) and proinflammatory cytokines in children with severe malnutrition and anemia. Methodology: levels of hemoglobin, transferrin, CRP and inflammatory markers such as cytokines IL–8, IL–1β, IL–6, IL–10, TNF–α and IL–12p70 were assessed in a group of 40 children, nutritional status was also evaluated.10 were classified with marasmus, 10 with kwashiorkor, 10 well nourish with anemia and 10 well nourish with no anemia. Results: C–reactive protein was significantly higher in undernourishment children than in well nourish children. Levels of proinflammatory cytokines were higher in children with kwashiorkor along by well nourish children with anemia, children with marasmus and well nourish children with no anemia. Hemoglobin was no correlated with levels of IL–8 (r=–0,409 p=0,009), IL–6 (r=–0,442 p=0,004) and IL–10 (r=–0,436 p=0,005). Conclusion:< malnourished children could develop an inflammatory condition presenting high levels of inflammatory markers such as C–reactive protein (CRP) and proinflammatory cytokines. These results suggest that proinflammatory cytokines may participate in the pathogenesis of anemia in malnourished or well nourished patients.Perspectivas en Nutrición Humana. 12/2008; 10(2):131-142.