Limits...
Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients.

Durastanti V, Lugaresi A, Bramanti P, Amato M, Bellantonio P, De Luca G, Picconi O, Fantozzi R, Locatelli L, Solda' A, Sessa E, Totaro R, Marino S, Zipoli V, Zorzon M, Millefiorini E - J Transl Med (2011)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurological Sciences, University La Sapienza, Viale dell'Università, 30, 00185, Rome, Italy. valentina.durastanti@uniroma1.it

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.

Show MeSH

Related in: MedlinePlus

A: neopterin serum levels as function of time and drug dose; B: kyn/trp ratio as function of time and drug dose. Neopterin production (A) and tryptophan degradation (as measured by kynurenine/tryptophan ratio) (B) in patients treated with 22 or 44 mcg of interferon beta-1a (IFNβ-1a), administered three times weekly via subcutaneous injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3102623&req=5

Figure 1: A: neopterin serum levels as function of time and drug dose; B: kyn/trp ratio as function of time and drug dose. Neopterin production (A) and tryptophan degradation (as measured by kynurenine/tryptophan ratio) (B) in patients treated with 22 or 44 mcg of interferon beta-1a (IFNβ-1a), administered three times weekly via subcutaneous injection.

Mentions: Neopterin and kyn/trp ratio profiles of each treatment group are shown in figure 1(A, B). In each treatment group, both neopterin concentration (p < 0.001) and kyn/trp ratio (p = 0.0013) increased over time compared to baseline. Mann-Whitney analyses showed that neopterin values were always higher in the HD-group vs the LD-one at each time point (p = 0.046) apart from months 21 and 24 of treatment period (TP). Conversely, while trends towards higher values of kyn/trp ratio in the HD-group were observed at numerous time points, group differences were not statistically significant at any time point with the exception of month-6 of TP (p < 0.05).


Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients.

Durastanti V, Lugaresi A, Bramanti P, Amato M, Bellantonio P, De Luca G, Picconi O, Fantozzi R, Locatelli L, Solda' A, Sessa E, Totaro R, Marino S, Zipoli V, Zorzon M, Millefiorini E - J Transl Med (2011)

A: neopterin serum levels as function of time and drug dose; B: kyn/trp ratio as function of time and drug dose. Neopterin production (A) and tryptophan degradation (as measured by kynurenine/tryptophan ratio) (B) in patients treated with 22 or 44 mcg of interferon beta-1a (IFNβ-1a), administered three times weekly via subcutaneous injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102623&req=5

Figure 1: A: neopterin serum levels as function of time and drug dose; B: kyn/trp ratio as function of time and drug dose. Neopterin production (A) and tryptophan degradation (as measured by kynurenine/tryptophan ratio) (B) in patients treated with 22 or 44 mcg of interferon beta-1a (IFNβ-1a), administered three times weekly via subcutaneous injection.
Mentions: Neopterin and kyn/trp ratio profiles of each treatment group are shown in figure 1(A, B). In each treatment group, both neopterin concentration (p < 0.001) and kyn/trp ratio (p = 0.0013) increased over time compared to baseline. Mann-Whitney analyses showed that neopterin values were always higher in the HD-group vs the LD-one at each time point (p = 0.046) apart from months 21 and 24 of treatment period (TP). Conversely, while trends towards higher values of kyn/trp ratio in the HD-group were observed at numerous time points, group differences were not statistically significant at any time point with the exception of month-6 of TP (p < 0.05).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurological Sciences, University La Sapienza, Viale dell'Università, 30, 00185, Rome, Italy. valentina.durastanti@uniroma1.it

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.

Show MeSH
Related in: MedlinePlus