title: Early proinflammatory cytokines and C‐reactive protein trends as predictors of outcome in invasive Aspergillosis.
abstract: BACKGROUND
  Monitoring treatment response in invasive aspergillosis is challenging, because an immunocompromised host may not exhibit reliable symptoms and clinical signs. Cytokines play a pivotal role in mediating host immune response to infection; therefore, the profiling of biomarkers may be an appropriate surrogate for disease status.
  
  
  METHODS
  We studied, in a cohort of 119 patients with invasive aspergillosis who were recruited in a multicenter clinical trial, serum interleukin (IL)-6, IL‐8, IL‐10, interferon‐γ, and C‐reactive protein (CRP) trends over the first 4 weeks of therapy and correlated these trends to clinical outcome parameters.
  
  
  RESULTS
  Circulating IL‐6 and CRP levels were high at initiation of therapy and generally showed a downward trend with antifungal treatment. However, subjects with adverse outcomes exhibited a distinct lack of decline in IL‐6 and CRP levels at week 1, compared with responders (P = .02, for both IL‐6 and CRP). Nonresponders also had significantly elevated IL‐8 levels (P = .001).
  
  
  CONCLUSIONS
  High initial IL‐8 and persistently elevated IL‐6, IL‐8, and CRP levels after initiation of treatment may be early predictors of adverse outcome in invasive aspergillosis. Cytokine and CRP profiles could be used for early identification of patients with a poor response to antifungal treatment who may benefit from more‐aggressive antimicrobial regimens.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Louis  A
authors.initials: L
authors.lastname: Chai
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Steven
authors.initials: S
authors.lastname: Teerenstra
authors.forename: Arul
authors.initials: A
authors.lastname: Earnest
authors.forename: Alieke G
authors.initials: AG
authors.lastname: Vonk
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Peter F
authors.initials: PF
authors.lastname: Troke
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D002097:C-Reactive Protein