アスパラギナーゼアレルギーに伴う液性免疫の亢進と薬剤耐性の特徴

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-058
• Main Authors: 原（野上）, 愛, 森, 映美加, 茶畑, 沙央里, 嶋田, 明, 見尾, 光庸
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: allergy; antiallergic agent; antibody; mast cell
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_1-B-P-058

L-Asparaginase (ASNase), a key drug in the treatment of childhood acute lymphoblastic leukemia, often causes allergic reactions and drug resistance. In this study, we examined the effect of cyclophosphamide (CY) on  the immune response to ASNase. Male BALB/c mice were sensitized by ASNase. CY was i.p. injected prior to ASNase sensitization. Total IgE level and ASNase activity in the sera were measured. RBL-2H3 cells were sensitized by the sera and stimulated by ASNase to determine β-hexosaminidase (β-Hex) release. Mice spleen cells were cultured for 48 hrs and cytokines in the medium were measured using a Bio-Plex Th1/Th2 assay kit. ASNase sensitization induced ear edema and increased serum IgE levels in mice. CY at 150 mg/kg augmented these responses. CY at 300 mg/kg increased serum IgE levels, but decreased ear edema and serum ASNase activity. Sera of CY 150 mg/kg-treated mice induced higher β-Hex release from RBL-2H3 cells than normal anti-ASNase sera, though those of CY 300 mg/kg-treated mice did not induce β -Hex release. After removing IgG from the sera of CY 300 mg/kg-treated mice, β -Hex release became higher than normally sensitized mice. ASNase sensitization induced a Th2-biased immune response, and the addition of CY further enhanced the Th2-bias in a dose-dependent manner.CY administration enhanced Th2-biased immune responses and increased IgE and IgG production in the ASNase-sensitized mice. These findings suggest that CY may play a role in the development of ASNase allergy and drug resistance.