title: Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients.
abstract: BACKGROUND
  Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months.
  
  
  METHODS
  RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests.
  
  
  RESULTS
  Neopterin (p < 0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p < 0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p < 0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation.
  
  
  CONCLUSIONS
  Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.
authors.affiliation: Department of Neurological Sciences, University La Sapienza, Viale dell'Università, 30, 00185, Rome, Italy. valentina.durastanti@uniroma1.it
authors.forename: Valentina
authors.initials: V
authors.lastname: Durastanti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Mariapia
authors.initials: M
authors.lastname: Amato
authors.forename: Paolo
authors.initials: P
authors.lastname: Bellantonio
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Luca
authors.forename: Orietta
authors.initials: O
authors.lastname: Picconi
authors.forename: Roberta
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Laura
authors.initials: L
authors.lastname: Locatelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Solda'
authors.forename: Edoardo
authors.initials: E
authors.lastname: Sessa
authors.forename: Rocco
authors.initials: R
authors.lastname: Totaro
authors.forename: Silvia
authors.initials: S
authors.lastname: Marino
authors.forename: Valentina
authors.initials: V
authors.lastname: Zipoli
authors.forename: Marino
authors.initials: M
authors.lastname: Zorzon
authors.forename: Enrico
authors.initials: E
authors.lastname: Millefiorini
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D007737:Kynurenine / Q000097:blood; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D019798:Neopterin / Q000096:biosynthesis* / Q000097:blood; D013997:Time Factors; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D007737:Kynurenine; D019798:Neopterin; D016899:Interferon-beta; D014364:Tryptophan; D000068556:Interferon beta-1a