Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection.
Activation of indoleamine-(2,3)-dioxygenase (IDO), an enzyme converting tryptophan to N-formyl-kynurenine, was found to be critical for induction of T-cell tolerance. In 45 HIV-seropositive patients we measured plasma tryptophan and kynurenine before and 6 months post-initiation of ART. Before ART, patients had decreased tryptophan and increased kynurenine levels compared to controls. During ART, average tryptophan concentrations increased, kynurenine decreased. Tryptophan degradation correlated with neopterin levels and with viral load but not with CD4 cell counts. The data support the concept that immune activation is the common background of IDO activation and could represent an important factor underlying T-cell hyporesponsiveness in HIV infection.
Neurauter
Gabriele
G
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria. gabriele.neurauter@uibk.ac.at
Zangerle
Robert
R
Widner
Bernhard
B
Quirchmair
Gisela
G
Sarcletti
Mario
M
Fuchs
Dietmar
D
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000096:biosynthesis; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000097:blood*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D019380:Anti-HIV Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase