L-ASParaginase (L-ASP) is a key drug in the treatment of childhood acute lymphoblastic leukemia. L-ASP often causes allergies. Cyclophosphamide (CY) used concomitantly with L-ASP, although the role of CY on L-ASP allergy is not known. In this study, using animal and in vitro models, we examined the effect of CY on L-ASP allergy.
Male BALB/c mice were sensitized by L-ASP with Al(OH)₃ gel on days 1 and 15. Then, the right ears of the mice were locally sensitized by i.d. injection of L-ASP. CY was i.p. injected on days –1 and 13. The serum was collected on day 27. Total IgE level in the serum was measured by ELISA. RBL-2H3 cells were sensitized by the serum and stimulated by L-ASP to determine β-hexosaminidase (β-Hex) release in vitro.
Both L-ASP-induced allergic ear edema and increase in serum IgE level were enhanced by CY at 150 mg/kg. On the other hand, at 300 mg/kg of CY, L-ASP-induced ear edema was much lower than 150 mg/kg, though IgE concentration in the serum was as high as CY 150 mg/kg. When RBL-2H3 cells were sensitized by anti-L-ASP serum, L-ASP challenge induced β-Hex release. Anti-L-ASP serum of CY 150 mg/kg-treated mice induced higher β-Hex release than normal anti-L-ASP serum, though that of CY 300 mg/kg-treated mice did not induce β-Hex release. After removing IgG from the serum of CY 300 mg/kg-treated mice using protein G Mag Sepharose, β-Hex release became higher than normally sensitized mice.
From the present results, it became clear that CY induced biphasic effects on L-ASP allergy in mice, enhancing it at low dosage and attenuating it at high dosage.