Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection.
Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.
Fuchs
D
D
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Möller
A A
AA
Reibnegger
G
G
Werner
E R
ER
Werner-Felmayer
G
G
Dierich
M P
MP
Wachter
H
H
D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006679:HIV Seropositivity / Q000097:blood; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D011863:Radioimmunoassay; D014364:Tryptophan / Q000097:blood*
D001708:Biopterins; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan