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PubMed2004

Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis.

BACKGROUND: Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity. AIM: To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity. METHODS: hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles. RESULTS: Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values. CONCLUSION: A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Adolescent↗
PubMed1997

Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation.

Our objective was to determine if placental histologic acute inflammation is related to maternal and fetal serum cytokine levels in preterm labor, using a data set previously constructed blinded to histopathologic information. To this goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and tocolytic failure were recruited. Maternal serum sampled during the active phase of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R), and interleukin 6 (IL-6) (T-Cell Diagnostics). Acute placental inflammation was scored by two groups blinded to clinical data, and the average scores analyzed for relationships to serum cytokine levels. Weighted kappa values, reflecting interobserver agreement in scoring of acute inflammation, were: amnion 0.84; choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73. Fetal levels of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with grades 0-2 (p = 0.022 and p = 0.023). Fetal levels of all three cytokines were higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01, and IL-6 p = 0.03). In contrast, maternal serum cytokine levels were not associated with presence or severity of histologic evidence of acute placental inflammation. Histologic acute inflammation was not related to duration of labor, interval from membrane rupture to delivery, and presence or duration of antibiotic therapy. We conclude that fetal serum, but not maternal serum cytokine levels, are correlated with histologic evidence of acute placental inflammation, and may reflect a predominant placental origin of the cytokines.

Acute Disease↗
PubMed1986

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members.

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known.

Adult↗
PubMed2002

Chronic intrauterine infection and inflammation in the preterm rabbit, despite antibiotic therapy.

OBJECTIVE: In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days. STUDY DESIGN: New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in the amniotic fluid were determined by bioassay. RESULTS: A total of 60 animals were inoculated with E coli. At the endpoint, uterine cultures were positive more commonly than in the fetus or amniotic fluid (41.8% vs 27.5% vs 17.3%, respectively), which was consistent with an ascending pathway of infection. Inflammation scores were similar in uterus and placenta but lower in fetal lung and absent in fetal brain (2.8 vs 3.1 vs 0.84 vs 0.0, respectively). Comparing the durations of delay in antibiotic administration, we found a significant increase in positive uterine cultures and a significant increase in histologic inflammation score with increasing delay. The proportion of dead pups within a litter was significantly associated with the log of the tumor necrosis factor-alpha concentration in amniotic fluid and the degree of histologic inflammation in the uterus, but not with amniotic fluid or other culture positivity. CONCLUSION: The administration of therapeutic doses of antibiotic does not consistently eradicate bacteria from the rabbit uterus nor, more importantly, from the fetus and the amniotic fluid. Obtaining a negative amniotic fluid culture does not exclude either infection in the decidua or the fetus or histologic inflammation with tumor necrosis factor-alpha elaboration.

Amniotic Fluid↗
PubMed2005

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor.

Changes in the lungs due to smoking include inflammation, epithelial damage, and remodeling of the airways. Airway inflammation is likely to play a critical role in the genesis and progression of tobacco smoke-induced airway disease. Soluble epoxide hydrolase (sEH) is involved in the metabolism of endogenous chemical mediators that play an important role in inflammation. Epoxyeicosatrienoic acids (EETs) have demonstrated antiinflammatory properties, and hydrolysis of these epoxides by sEH is known to diminish this activity. To examine whether acute tobacco smoke-induced inflammation could be reduced by a sEH inhibitor, 12-(3-adamantane-1-yl-ureido)-dodecanoic acid n-butyl ester was given by daily s.c. injection to spontaneously hypertensive rats exposed to filtered air or tobacco smoke for a period of 3 days (6 h/day). Acute exposure to tobacco smoke significantly increased by 3.2-fold (P <0.05) the number of cells recovered by bronchoalveolar lavage. The sEH inhibitor significantly decreased total bronchoalveolar lavage cell number by 37% in tobacco smoke-exposed rats with significant reductions noted in neutrophils, alveolar macrophages, and lymphocytes. A combination of sEH inhibitor and EETs was more significant in its ability to further reduce tobacco smoke-induced inflammation compared with the sEH inhibitor alone. The sEH inhibitor led to a shift in some plasma epoxides and diols that are consistent with the hypothetical action of these compounds. We conclude that an sEH inhibitor, in the presence or absence of EETs, can attenuate, in part, inflammation associated with acute exposure to tobacco smoke.

Animals↗
PubMed1991

Inhibition of acute inflammation in the periphery by central action of salicylates.

Understanding of the antiinflammatory actions of nonsteroidal drugs is incomplete, but these actions are believed to occur in the periphery, without any contribution from the central nervous system. Recent research on the antipyretic antiinflammatory neuropeptide alpha-melanocyte-stimulating hormone indicates that it can act centrally to inhibit peripheral inflammation; this raises the possibility that other agents, such as nonsteroidal antiinflammatory drugs, may have similar activity. In the present research both lysine acetylsalicylate and sodium salicylate inhibited edema, induced in the mouse ear by topical application of picryl chloride, when injected into the lateral cerebral ventricle. This inhibitory activity on a measure of acute inflammation was not due to escape of the drugs into the periphery, because systemic injection of doses that were effective centrally did not affect inflammation. In contrast, central administration of a dose of indomethacin that was antiinflammatory when given intraperitoneally did not inhibit peripheral inflammation. Thus indomethacin apparently lacks the central antiinflammatory action of the salicylates. This observation, plus our inability to demonstrate either an antiinflammatory effect of intracerebroventricular dexamethasone, a prostaglandin inhibitor, or a pro-inflammatory influence of prostaglandin E2, suggests that prostaglandins are not important to central modulation of inflammation. The results indicate that, in addition to having central influences on fever and pain, salicylates can act within the brain to inhibit acute inflammation in the periphery.

Animals↗
PubMed2002

Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation.

Acute and chronic inflammation cause many changes in total body iron metabolism including the sequestration of iron in phagocytic cells of the reticuloendothelial system. This change in iron metabolism contributes to the development of the anemia of inflammation. MTP1, the duodenal enterocyte basolateral iron exporter, is also expressed in the cells of the reticuloendothelial system (RES) and is likely to be involved in iron recycling of these cells. In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation. The down-regulation of splenic expression of MTP1 by inflammation was also observed in a Leishmania donovani model of chronic infection. The response of MTP1 to lipopolysaccharide (LPS) requires signaling through the LPS receptor, Toll-like receptor 4 (TLR4). In mice lacking TLR4, MTP1 expression is not altered in response to LPS. In addition, mice lacking tumor necrosis factor-receptor 1a respond appropriately to LPS with down-regulation of MTP1, despite hyporesponsiveness to tumor necrosis factor-alpha signaling, suggesting that this cytokine may not be required for the LPS effect. We hypothesize that the iron sequestration in the RES system that accompanies inflammation is because of down-regulation of MTP1.

Animals↗
PubMed2005

Micronutrients in childhood and the influence of subclinical inflammation.

In the present paper biomarkers of micronutrient status in childhood and some of the factors influencing them, mainly dietary intake, requirements and inflammation will be examined. On a body-weight basis the micronutrient requirements of children are mostly higher than those of an adult, but most biomarkers of status are not age-related. A major factor that is often overlooked in assessing status is the influence of subclinical inflammation on micronutrient biomarkers. In younger children particularly the immune system is still developing and there is a higher frequency of sickness than in adults. The inflammatory response rapidly influences the concentration in the blood of several important micronutrients such as vitamin A, Fe and Zn, even in the first 24 h, whereas dietary deficiencies can be envisaged as having a more gradual effect on biomarkers of nutritional status. The rapid response to infection may be for protective reasons, i.e. conservation of reserves, or by placing demands on those reserves to mount an effective immune response. However, because there is a high prevalence of disease in many developing countries, an apparently-healthy child may well be at the incubation stage or convalescing when blood is taken for nutritional assessment and the concentration of certain micronutrient biomarkers will not give a true indication of status. Most biomarkers influenced by inflammation are known, but often they are used because they are convenient or cheap and the influence of subclinical inflammation is either ignored or overlooked. The objective of the present paper is to discuss: (1) some of the important micronutrient deficiencies in childhood influenced by inflammation; (2) ways of correcting the interference from inflammation.

Adolescent↗
PubMed2004

Clinical and cytopathologic correlation in chronic inflammations of the orbit and ocular adnexa: a review of 55 cases.

Fine-needle aspiration cytology has been used for the diagnosis of neoplastic lesions of the orbit and ocular adnexa with some success. However, inflammatory conditions have not received much attention. This is a retrospective study of fine-needle aspirations of chronic inflammations of the orbit and ocular adnexa over a 15-year period from January 1988 through December 2002. Clinical records and stained smears were reviewed. There were 55 chronic inflammations, presenting as masses, cysts, abscesses, discharging sinuses and dermal plaques and nodules. Forty-two were granulomatous inflammations comprising chalazion (18), tuberculosis (5), Cysticercus cellulosae (3), ruptured epidermal cysts (2), actinomycosis (1) and leprosy (13). Thirteen patients had chronic non-specific inflammations. Fine-needle aspiration cytology is a useful diagnostic procedure in chronic inflammations of the ocular adnexa. Specific diagnosis is possible in many granulomatous inflammations, allowing appropriate, individualized therapy to be initiated.

Biopsy, Fine-Needle↗
PubMed1999

Assessment of terminal ileal and colonic inflammation in Crohn's disease with 99mTc-WBC.

We evaluated the sensitivity and specificity of Technetium-99m (99mTc)-white blood cell (WBC) for identifying terminal ileum inflammation in children with Crohn's disease (CD). In 40 children, total colonoscopy was done within a few days of a 99mTc-WBC scan carried out to evaluate the inflammation in children with CD. In 38 patients the intensity and the location of inflammation shown on the 99mTc-WBC scan of the colon were similar to the biopsy result of the colonoscopy. The sensitivity of the 99mTc-WBC scan was 97% in assessing colonic inflammation compared with colonoscopy. The 99mTc-WBC scan allowed evaluation of inflammation in the terminal ileum in 21 patients in whom the endoscopist did not cannulate the terminal ileum. Of the 19 patients in whom the terminal ileum was visualized endoscopically (14) or surgically (5), the 99mTc-WBC scan findings showed a similar degree of inflammation in 17. The 99mTc-WBC scan was abnormal in 10 of these 21 children in whom the gastroenterologist did not reach the terminal ileum. In these children with no ileoscopy the results of the 99mTc-WBC scan were consistent with the laboratory values, the gastroenterologist's clinical assessment and with long-term clinical follow-up. Finally, the 99mTc-WBC scan of 83 controls did not reveal any false-positive findings in the terminal ileum (colonoscopy result available in 30 controls). When total colonoscopy or ileoscopy is not performed or when contrast radiography is negative or unable to differentiate CD from lymphoid nodular hyperplasia, scintigraphy can demonstrate the presence of ileitis and/or colitis.

Adolescent↗
PubMed1998

Nonspecific inflammation inhibits adenovirus-mediated pulmonary gene transfer and expression independent of specific acquired immune responses.

Replication-deficient adenovirus vectors (Avs) have shown high-efficiency gene transfer in a variety of animal models, but demonstrated lower than expected efficiency in the intensely inflammatory milieu of the respiratory tract of individuals with cystic fibrosis (CF). Specific acquired immune responses directed at adenovirus capsid proteins are known to limit the duration of transgene expression and the effectiveness of vector readministration. In these models, however, nonspecific inflammation is also frequently noted to accompany specific immune responses. Because inflammation can occur early after Av administration, we hypothesized that inflammation may block Av-mediated gene transfer in the lung independent of specific immune responses. To evaluate this hypothesis, we measured pulmonary gene transfer and expression in the absence or presence of the potent antiinflammatory agent dexamethasone. To address and eliminate concerns over the potentially confounding effects of systemic, vector-specific acquired immune responses, evaluations were confined to a 3-day period following Av administration and were carried out, in parallel, in normal and immunodeficient (athymic) mice. Dexamethasone significantly reduced Av-associated inflammation in all animals as measured by a significant reduction of blinded, quantitative lung histopathology scores and by reduced proinflammatory cytokine release. Concomitant with reduced inflammation, gene transfer efficiency was significantly increased in both normal and immunodeficient animals as measured by transgene product activity (beta-galactosidase) in total lung homogenates 3 days after vector administration. This finding could not be explained by a direct effect of dexamethasone on transgene specific activity. To begin to understand the molecular mechanisms of Av-induced inflammatory responses, lung levels of the chemoattractive chemokines MIP-2, MIP-1alpha, and MCP-1 were quantified. All were elevated significantly in Av-exposed animals. Dexamethasone reduced levels of MCP-1 and MIP-1alpha, but not MIP-2, consistent with the observed pattern of inflammatory cell changes. Expression of several proinflammatory cytokines including TNF-alpha, IL-6, IL-1beta, and IFN-gamma were also elevated in Av-exposed animals and modulated by dexamethasone. These observations demonstrate that nonspecific inflammation is an important determinant of the efficiency of in vivo pulmonary gene transfer and expression independent of specific immune responses and may have important implications for human gene therapy for diseases of the lung.

Adenoviridae↗
PubMed2001

Association between physical activity and markers of inflammation in a healthy elderly population.

Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.

Aged↗
PubMed2004

Prostate carcinogenesis and inflammation: emerging insights.

Prostate cancer remains a significant health concern for men throughout the world. Recently, there has developed an expanding multidisciplinary body of literature suggesting a link between chronic inflammation and prostate cancer. In support of this hypothesis, population studies have found an increased relative risk of prostate cancer in men with a prior history of certain sexually transmitted infections or prostatitis. Furthermore, genetic epidemiological data have implicated germline variants of several genes associated with the immunological aspects of inflammation in modulating prostate cancer risk. The molecular pathogenesis of prostate cancer has been characterized by somatic alterations of genes involved in defenses against inflammatory damage and in tissue recovery. A novel putative prostate cancer precursor lesion, proliferative inflammatory atrophy, which shares some molecular traits with prostate intraepithelial neoplasia and prostate cancer, has been characterized. Here, we review the evidence associating chronic inflammation and prostate cancer and consider a number of animal models of prostate inflammation that should allow the elucidation of the mechanisms by which prostatic inflammation could lead to the initiation and progression of prostate cancer. These emerging insights into chronic inflammation in the etiology of prostate carcinogenesis hold the promise of spawning new diagnostic and therapeutic modalities for men with prostate cancer.

Animals↗
PubMed2005

Inflammation-dependent changes in alpha2,3-, alpha2,6-, and alpha2,8-sialic acid glycotopes on serum glycoproteins in mice.

The expression of acute-phase serum proteins increases in response to inflammatory stimuli. Most of these proteins are glycoproteins that often contain sialic acids (Sia). It is unknown, however, how the expression of Sia in these glycoproteins changes during inflammation. This study demonstrates changes in the alpha2,3-, alpha2,6-, and alpha2,8-Sia glycotopes on serum glycoproteins in response to turpentine oil-induced inflammation, based on lectin- and immunoblot analyses by using sialyl linkage-specific lectins, Maackia amurensis for the alpha2,3-Sia glycotope and Sambucus sieboldiana for the alpha2,6-Sia glycotopes, and monoclonal antibody 2-4B (mAb.2-4B) recognizing the di- and oligomers of the alpha2,8-Neu5Gc residue. There was an increase in a limited number of sialoglycoproteins containing the alpha2,3-, alpha2,6-, or alpha2,8-Sia glycotopes. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression profiles of mRNAs for the known sialyltransferases in mouse liver during inflammation indicated the up-regulated expression of beta-galactoside alpha2,3-sialyltransferases (ST3Gal I and ST3Gal III) and beta-N-acetylgalactosaminide alpha2,6-sialyltransferase (ST6GalNAc VI) as well as beta-galactoside alpha2,6-sialyltransferase (ST6Gal I) mRNAs. Notably, ST3Gal I and III and ST6GalNAc VI are involved in the synthesis of the alpha2,3- and alpha2,6-Sia glycotopes on O-glycan chains and possibly on gangliosides, whereas ST6Gal I is specific for N-glycan chains. These results provide evidence for the inflammation-induced expression of sialyl glycotopes in serum glycoproteins. We demonstrated that inflammation significantly increased the expression of an unknown 32-kDa glycoprotein containing the alpha2,8-Sia glycotope. The mechanism for the increase in glycoprotein in inflamed mouse serum remains to be examined, as mRNA expression for all of the alpha2,8-sialyltransferases (ST8Sia I-VI) was unchanged during inflammation.

Acute-Phase Proteins↗
PubMed1999

Possible role of ovarian epithelial inflammation in ovarian cancer.

Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

Asbestos↗
PubMed2002

The malnutrition, inflammation, and atherosclerosis (MIA) syndrome -- the heart of the matter.

The majority of patients starting dialysis already have signs of advanced atherosclerosis, and the risk factors for cardiovascular morbidity and mortality seen in patients with end-stage renal disease (ESRD) develop with the disease progression. Therefore, the predialysis period is the ideal time to start therapeutic interventions. Traditional risk factors alone may not adequately predict cardiovascular disease (CVD) outcome in patients with ESRD. Inflammation has been identified as playing a key role in atherosclerotic CVD. Pro-inflammatory cytokines are pivotal to the inflammation that is associated with malnutrition and atherosclerosis in ESRD. Malnutrition may worsen patient outcome by aggravating existing inflammation and heart failure, accelerating atherosclerosis and increasing susceptibility to infection. Atherosclerosis is itself a major risk factor for CVD mortality. Moreover, inflammation is associated with congestive heart failure. Strong associations between malnutrition, inflammation and atherosclerosis in this patient population suggest the presence of a syndrome we have called malnutrition, inflammation, and atherosclerosis (MIA), which is associated with an exceptionally high mortality rate.

Arteriosclerosis↗
PubMed2003

Anaemia and inflammation: what are the implications for the nephrologist?

End-stage renal disease (ESRD) is characterized by a high mortality rate, which is mainly caused by cardiovascular disease. In patients with ESRD, high levels of pro-inflammatory cytokines and increased oxidative stress are common features and may contribute to the development of malnutrition, anaemia, resistance to recombinant human erythropoietin (epoetin) and atherosclerosis. The onset of inflammation is multi-factorial and is a predictor of poor outcome in ESRD. Although the inflammation may reflect the underlying cardiovascular disease, the acute-phase response may also contribute to both oxidative stress and progressive vascular injury. The acute-phase response in these patients may be influenced by a number of factors, and possibly the dialysis procedure itself. Inflammation and the acute-phase response interact with the haematopoietic system at several levels, resulting in reduced erythropoiesis, accelerated destruction of erythrocytes and blunting of the reactive increase in erythropoietin in response to reduced haemoglobin levels. In patients with ESRD, epoetin resistance has been linked with inflammation, which is often associated with a state of functional iron deficiency. Patients with ESRD are thought to have a reduced capacity in their control of oxidative stress and there is evidence that suggests that a relationship may exist between inflammation, oxidative stress and the treatment of anaemia with epoetin. Controlled trials are needed before evidence-based recommendations for the management of inflammation-induced anaemia and resistance to epoetin can be defined.

Anemia↗
PubMed2006

Early markers of inflammation in a high angiotensin II state--results of studies in Bartter's/Gitelman's syndromes.

BACKGROUND: Inflammation has been increasingly recognized as playing a critical role in hypertension and atherosclerosis as reflected by overexpression and increased production of a variety of pro-inflammatory mediators. As angiotensin II (Ang II) also plays a major role in these diseases, the relationship between inflammation and Ang II has drawn increasing scrutiny. This study explores Ang II effects in Bartter's and Gitelman's syndromes (BS/GS) which do not develop hypertension and related cardiovascular remodelling and atherosclerosis, in spite of high Ang II levels and activation of the renin-angiotensin-aldosterone system while the NO system is up-regulated. METHODS: We evaluated the plasma levels of inflammation-associated markers, C-reactive protein (CRP), serum amyloid A (SAA), vascular cell adhesion molecules (VCAM) and intercellular adhesion molecules (ICAM), and the inflammation-related cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) using immunonephelometric and ELISA-based assays. RESULTS: The study demonstrated that all markers of inflammation except TNF-alpha, were unchanged in BS/GS (2.51+/-0.62 mg/l in BS/GS vs 1.7+/-0.6 in controls for CRP; 4.56+/-1.09 mg/l in BS/GS vs 4.51+/-1.0 for SAA; 1.84+/-0.27 ng/l in BS/GS vs 2.1+/-0.3 for IL-6; 449+/-83 ng/ml in BS/GS vs 410+/-92 for VCAM and 234+/-26 ng/ml in BS/GS vs 185+/-22 for ICAM), while TNF-alpha was increased (10.5+/-2.03 vs 3.68+/-0.2, P = 0.0001). CONCLUSIONS: The results of this study stress the critical role played by Ang II in controlling vascular biology including inflammation-related processes as well as highlighting the utility of BS/GS in investigating these pathways.

Acute-Phase Proteins↗