title: Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity.
abstract: The cardiovascular mortality rate is unacceptably high in patients with end-stage renal disease (ESRD), which suggests an accelerated atherogenic process. The cause(s) of the accelerated atherogenesis in ESRD patients are not known, though recent studies suggest that persistent infection, such as Chlamydia pneumoniae, and proinflammatory cytokines may contribute. Forty-five ESRD patients (26 men) aged 51 +/- 2 years was studied at a time-point close to start of dialysis treatment and again after about 12 months of dialysis treatment. By using noninvasive B-mode ultrasonography, we evaluated changes in a surrogate marker of atherosclerosis, calculated intima media (cIM) area, in the common carotid artery. C-reactive protein (CRP), S-albumin, and interleukin-6 (IL-6) assessed the presence of an inflammatory reaction. We also measured C pneumoniae antibodies by microimmunofluorescence, nutritional status by subjective global assessment, lipid parameters, smoking habits, and the presence of comorbidity close to the start of dialysis. No significant changes in the prevalence of carotid plaques or the mean cIM area were observed during the first 12 months of dialysis. However, because some patients showed marked increases in the cIM area during only 12 months of dialysis we divided the patients into 2 groups: 23 nonprogressors ((delta)cIM area -2.7 +/- 0.4 mm2) and 22 progressors ((delta)cIM area 3.6 +/- 0.7 mm2). Sex, age, body mass index, comorbidity, blood lipid levels, S-albumin, and CRP levels did not differ significantly between the 2 groups. On the other hand, progressors had a significantly elevated basal median level of IL-6 (5.7 versus 3.1 pg/mL; P < 0.05) and an increased prevalence of positive (> or 1/64) immunoglobulin (Ig) A antichlamydia antibodies (59% versus 17%; P < 0.01) compared with nonprogressors. A significant positive (R = 0.41; P < 0.01) correlation was found between Log IL-6 and changes in the cIM area during 12 months of dialysis. In a stepwise multiple regression model, Log IL-6 did predict, independently (P < 0.01) of traditional risk factors and C pneumoniae antibodies, changes in the cIM area. These data suggest that a persistent chlamydial infection stimulates IL-6 levels, which in turn may be involved in the pathogenesis of accelerated carotid atherosclerosis in dialysis patients.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Karolinska Institutet and Huddinge University Hospital, Stockholm, Sweden. peter.stenvinkel@klinvet.ki.se
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Tomas
authors.initials: T
authors.lastname: Jogestrand
mesh_terms: D001161:Arteriosclerosis / Q000175:diagnosis* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000209:etiology; D023521:Chlamydophila Infections / Q000175:diagnosis* / Q000209:etiology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification*; D018450:Disease Progression; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D006435:Renal Dialysis / Q000009:adverse effects*; D012698:Serologic Tests; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6