Urinary adenosine and aminoimidazolecarboxamide excretion in methotrexate-treated patients with psoriasis.
BACKGROUND
We hypothesized that low-dose methotrexate treatment for patients with psoriasis would block purine biosynthesis at the step catalyzed by aminoimidazolecarboxamide (AICA) ribotide transformylase and would inhibit adenosine metabolism as evidenced by increased urinary levels of AICA and adenosine, respectively. Eight patients collected a 24-hour urine specimen on the day before their methotrexate dose and the next day during their methotrexate dose. Eight age- and sex-matched controls also collected a 24-hour urine sample. Urinary AICA and adenosine were assayed by spectrophotometric and radioimmune assays, respectively; means are reported as micromole per millimole of creatinine and were compared by the paired t test (1-tailed).


METHODS
Mean AICA excretion increased from 1.30 micromol/mmol on the day before to 1.85 micromol/mmol on the day during methotrexate dosing (P<.01). Mean adenosine values increased from 0.68 to 1.07 micromol/mmol, (P<.03). Controls had mean AICA and adenosine levels of 1.29 and 0.50 micromol/mmol, respectively. During the day of methotrexate dosing, patients had higher mean AICA and adenosine levels when compared with controls (P<.01). Mean AICA levels increased from 1.36 to 2.06 micromol/mmol (P<.025), and mean adenosine levels increased from 0.72 to 1.25 micromol/mmol (P<.025) in 5 patients showing improvement in clinical disease activity. In contrast, 3 patients with no change or worsening in clinical disease activity had smaller increases.


CONCLUSIONS
Methotrexate treatment of patients with psoriasis inhibits AICA ribotide transformylase and adenosine metabolism. Since adenosine is a T-lymphocyte toxin, it may be partially responsible for the immunosuppressive effect.
Baggott
J E
JE
Department of Nutrition Sciences, School of Health Related Professions, University of Alabama, Birmingham 35294-3360, USA.
Morgan
S L
SL
Sams
W M
WM
Linden
J
J
D000241:Adenosine / Q000652:urine*; D000328:Adult; D000368:Aged; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D011565:Psoriasis / Q000188:drug therapy* / Q000652:urine*; D012265:Ribonucleotides / Q000652:urine*
D005493:Folic Acid Antagonists; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D019877:Hydroxymethyl and Formyl Transferases; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; C031143:AICA ribonucleotide; D000241:Adenosine; D008727:Methotrexate