Tryptophan concentrations increase in cerebrospinal fluid and blood after zidovudine treatment in patients with HIV type 1 infection.
Cerebrospinal fluid (CSF) and blood concentrations of indoleamines and catecholamines were analyzed in 14 HIV-1-seropositive individuals before antiviral treatment with zidovudine, after 3-14 months of treatment, and, in 8 of the patients, also after 14-30 months. The median pretreatment concentrations of tryptophan in CSF and blood were low (224 ng/ml and 6.0 micrograms/ml, respectively), but an increase in these values by an average of 40% in CSF and 23% in blood was seen after 3-14 months of zidovudine treatment (p < 0.01) and remained undiminished after 14-30 months of treatment. No significant change was observed in the 5-hydroxytryptamine (5-HT, serotonin) level in blood or in the CSF concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA). The CSF concentrations of the noradrenalin metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) had decreased by 12% on average (p < 0.01) by the time of the second follow-up, that is, after 14-30 months of zidovudine treatment. A decrease in neopterin during antiretroviral treatment correlated with an increase in tryptophan (p < 0.01). The data suggest that an association between decreased immune stimulation and reduced tryptophan degradation in patients treated with zidovudine.
Gisslén
M
M
Department of Infectious Diseases, University of Göteborg, Sweden.
Larsson
M
M
Norkrans
G
G
Fuchs
D
D
Wachter
H
H
Hagberg
L
L
D000328:Adult; D000368:Aged; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D019798:Neopterin; D012701:Serotonin / Q000097:blood; D014364:Tryptophan / Q000097:blood* / Q000134:cerebrospinal fluid*; D015215:Zidovudine / Q000627:therapeutic use*
D007074:Immunoglobulin G; D001708:Biopterins; D012701:Serotonin; D015215:Zidovudine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D019798:Neopterin; D014364:Tryptophan; D006719:Homovanillic Acid