title: IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults.
abstract: BACKGROUND
  neopterin is a monocyte/macrophage-derived immune activation marker and its levels increase with age. Frailty is an important clinical syndrome of old age. Previous studies have shown significant association between elevated interleukin-6 (IL-6) levels and frailty. The objective of this study was to evaluate IL-6-independent association of serum neopterin levels with prevalent frailty.
  
  
  METHODS
  this is a cross-sectional study in community-dwelling older adults recruited from residential and retirement communities in Baltimore, MD, USA. Frailty was determined using validated screening criteria. Serum neopterin and IL-6 levels were measured using standard enzyme-linked immunosorbent assay. Pearson correlation and multivariate linear regression analysis was performed to assess the relationship between log(neopterin) and log(IL-6). Odds ratios (ORs) for frailty were calculated using log(neopterin) and log(IL-6) as continuous measures and across tertiles of neopterin and IL-6 levels, adjusting for age, race, sex, education and body mass index.
  
  
  RESULTS
  one hundred and thirty-three individuals with a mean age of 84 years (range 72-97) completed the study. Neopterin levels were significantly higher in frail older adults than those in non-frail controls [median: 8.94 versus 8.35 nM, respectively, P < 0.001 t-test on log(neopterin)]. Log(neopterin) was significantly associated with prevalent frailty, adjusting for log(IL-6). Participants in the top tertile of neopterin had OR of 3.80 [95% confidence interval (CI) = 1.36-10.6, P < 0.01] for frailty. As expected, participants in the top tertile of IL-6 had OR of 3.29 (95% CI = 1.21-7.86, P < 0.05) for frailty. Log(neopterin) correlated with log(IL-6) (correlation coefficient = 0.19, P < 0.05). Moreover, OR for participants in the top neopterin tertile remained significant after adjusting for IL-6 (OR = 3.97, 95% CI = 1.15-13.72, P < 0.05).
  
  
  CONCLUSIONS
  elevated neopterin levels had IL-6-independent association with prevalent frailty, suggesting potential monocyte/macrophage-mediated immune activation in the frail elderly.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.forename: Xinping
authors.initials: X
authors.lastname: Tian
authors.forename: Amy
authors.initials: A
authors.lastname: Matteini
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hughes
authors.forename: Alka
authors.initials: A
authors.lastname: Jain
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: Neal S
authors.initials: NS
authors.lastname: Fedarko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D016330:Frail Elderly; D006801:Humans; D057187:Independent Living; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016014:Linear Models; D016015:Logistic Models; D019798:Neopterin / Q000097:blood*; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D019798:Neopterin