Studies on toluene diisocyanate (TDI)-induced delayed type hypersensitivity.

The toluene diisocyanate (TDI)-induced delayed type hypersensitivity reaction (DTH) in the ear of male mice was investigated and compared with the picryl chloride (PC)-induced one. The results obtained were as follows: 1) When 1% TDI solution (20 microliters/ear) as a challenging concentration was used for 7 weeks-old ICR mice, distinct ear swelling was observed in every group sensitized with various concentrations (1-5%, 100 microliters/animal) of TDI solution, and the swelling rate was the same or higher than that of PC-induced DTH. 2) Five, 7 and 13 weeks-old ICR mice showed a similar high response in TDI-induced DTH, whereas the reactivity of 16 weeks-old ICR mice was significantly lower than that of the above-mentioned younger mice. 3) In both TDI- and PC-induced DTH, ICR and BALB/c mice showed a similar high response, whereas the reactivity of ddY mice was significantly lower. The relationship between increase of the ear swelling and the amount of Evans' blue dye leaked being regarded as the intensity of its vasopermeability was also studied. The results obtained were as follows: 1) The dye leakage reached the maximum at 20 hr after challenge in sensitized mice. This peak preceded slightly that of the ear swelling (25 hr after challenge). 2) A positive correlation was observed between ear swelling and dye leakage (r = 0.87, P less than 0.01). The effects of dexamethasone (DX) and indomethacin (IM) were investigated with the TDI-induced DTH model. The DTH reaction was suppressed significantly by both drugs, but the suppressive effects of DX were higher than that of IM. All the above results indicate that the TDI-induced DTH model in mice taking dye leakage as an index may be useful for evaluation of drugs for disorders derived from DTH reactions.