Allopurinol increases ear swelling and mortality in a dinitrofluorobenzene-induced contact hypersensitivity mouse model.
The immunomodulatory effects of allopurinol were investigated in a mouse contact hypersensitivity model. Allopurinol caused a time- and dose-dependent lethal effect in dinitrofluorobenzene (DNFB)-sensitized mice. Furthermore, allopurinol markedly increased ear swelling in the remaining mice. In contrast, TMX-67, a newly synthesized xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitor, had almost no effect on DNFB-sensitized mice. Allopurinol reduced both the spleen weight and white blood cell count in DNFB-sensitized mice without affecting the T cell subset of splenocytes. The production of interferon (IFN)-gamma, in the splenocytes of DNFB-sensitized mice was reduced by allopurinol administration. Death due to allopurinol was much lower in the non-sensitized mice than in the DNFB-sensitized mice. These findings indicate that allopurinol may interact with DNFB to enhance its toxicity and allopurinol might also modulate or enhance the inflammatory effect of DNFB. Also, DNFB may cause metabolic alterations via inflammation, leading to enhanced allopurinol toxicity.
Horiuchi
H
H
Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for BioMedical Research, Hino, Tokyo, Japan.
Ota
M
M
Kitahara
S
S
Ohta
T
T
Kiyoki
M
M
Komoriya
K
K
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004195:Disease Models, Animal; D004423:Ear / Q000503:physiopathology*; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate
D016207:Cytokines; D000493:Allopurinol; D004139:Dinitrofluorobenzene