Early proinflammatory cytokines and C‐reactive protein trends as predictors of outcome in invasive Aspergillosis.
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.
Chai
Louis  A
L
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Netea
Mihai G
MG
Teerenstra
Steven
S
Earnest
Arul
A
Vonk
Alieke G
AG
Schlamm
Haran T
HT
Herbrecht
Raoul
R
Troke
Peter F
PF
Kullberg
Bart Jan
BJ
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
D000935:Antifungal Agents; D016207:Cytokines; D002097:C-Reactive Protein