The effects of allopurinol on immune function in normal BALB/c and SCID mice

Abstract

To clarify the relationship between purine metabolism and immunity, the in vivo immunosuppressive effects of allopurinol (AL), a xanthinoxidase (XO) inhibitor, were studied using normal BALB/c and severe combined immunodeficient (SCID) mice. Following AL administration for 14 weeks (long term), a decreased immune response to ovalbumin (OVA) in the peripheral blood was observed in normal mice, which might not be only due to direct B cell suppression but also due to suppression of helper T cell function. In the SCID mice, there was a markedly late and reduced recovery of surface immunoglobulin (sIg) positive cells, which are markers for mature B lymphocytes, in the peripheral blood after AL administration. The total immunoglobulin G (IgG) titers in the AL treated group were significantly lower than in the control group 6 weeks after stem cell transfer, but increased until there was no difference in the titers between the two groups at week 14. CD4 positive helper T cells and CD8 positive T cells were slow to recover, though these gradually recovered to reach normal levels in the mature stage. These data suggest that the administration of AL may modulate B cell and T cell responses in OVA-immunized antibody formation. Furthermore, this study showed that AL could influence immune functions during the pre-natal and developmental periods and that its effects might differ according to the stages of maturity of the immune cells.