Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Look, M.P. et al.

Look, Altfeld, Kreuzer, Riezler, Stabler, Allen, Sauerbruch, Rockstroh,

Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor receptor p75 in serum during highly active antiretroviral therapy of HIV type 1 disease.

The chronic immune activation state in HIV disease leads to increased activity of the rate-limiting tryptophan-kynurenine pathway enzyme indoleamine 2,3-dioxygenase (2,3-IDO), thereby increasing the formation of neurotoxic tryptophan metabolites such as kynurenine and quinolinic acid. We investigated whether highly active antiretroviral therapy (HAART) (median duration, 100 days; range, 50-188 days) lowers serum levels of these metabolites in HIV-infected individuals and if so, whether this was paralleled by changes in a surrogate marker for immune activation, i.e., soluble tumor necrosis factor receptor p75 (sTNFR p75) concentrations. Baseline quinolinic acid (848 nM, 95% CI 567-1130 vs. 303 nM, 95% CI 267.1-339.5) and kynurenine (4.1 microM, 95% CI 3.3-4.9 vs. 2.7 microM, 95% CI 2.4-2.9) concentrations as well as the mean kynurenine-to-tryptophan ratio (108.2, 95% CI 76.1-140.4 vs. 51.4, 95% CI 47.6-55.3) in 17 HIV-1-infected outpatients (7 with AIDS) were significantly higher than those in 55 healthy age-matched controls (p < 0.01), respectively. Serum quinolinic acid concentrations in 14 of 17 patients decreased (mean, -44.4%) during HAART in comparison with baseline (471.2 nM, 95% CI 288-654.3; p = 0. 022). Thirteen of these 14 patients also had decreases in sTNFR p75 concentrations. Overall, the mean sTNFR p75 concentration decreased by 36.3% (13.5 ng/ml, 95% CI 9.3-17.8 vs. 8.6 ng/ml, 95% CI 5.9-11. 4; p = 0.01, n = 17). Reduction in viral load through HAART and subsequent mitigation of the pathological immune activation state in HIV disease may have reduced 2,3-IDO over activation. This eventually led to a decrease in quinolinic acid formation. The parallel reduction of the immune activation marker sTNFR p75 supports this hypothesis.[1]

References

Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor receptor p75 in serum during highly active antiretroviral therapy of HIV type 1 disease. Look, M.P., Altfeld, M., Kreuzer, K.A., Riezler, R., Stabler, S.P., Allen, R.H., Sauerbruch, T., Rockstroh, J.K. AIDS Res. Hum. Retroviruses (2000) [Pubmed]

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