Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch-Nyhan syndrome.
The mixed lymphocyte reaction of Lesch-Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6-MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6-MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63.9% and 30.6% for 6-MP. The difference in inhibitory activity between azathioprine and 6-MP was reduced when normal stimulator lymphocytes were cultured with HGPRT deficient responder lymphocytes in the MLR. These results provide very strong evidence that the nucleotide metabolites of azathioprine and 6-MP are unnecessary for immunosuppression. They also suggest that azathioprine and 6-MP interfere with antigenic triggering of the MLR.
Szawlowski
P W
PW
Al-Safi
S A
SA
Dooley
T
T
Maddocks
J L
JL
D000293:Adolescent; D001379:Azathioprine / Q000494:pharmacology*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007926:Lesch-Nyhan Syndrome / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology*
D015122:Mercaptopurine; D007041:Hypoxanthine Phosphoribosyltransferase; D001379:Azathioprine