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Respiratory sensitization to certain low molecular weight chemicals is a big concern for workers, but unfortunately there are no validated animal models to allow identification of sensitizing chemicals in the environment. In the present study, dermally sensitized and intratracheally challenged mice were used to investigate effective indicators of respiratory sensitizers. Changes in levels of total serum IgE and nine cytokines (G-CSF, IL-4, IL-5, IL-6, IL-12(p70), IL-13, IFN-γ, MCP-1 and TNF-α) in bronchoalveolar lavage fluid (BALF) were analyzed in BALB/c mice exposed to respiratory sensitizers (phthalic anhydride (PA); diphenylmethane-4,4'-diisocyanate (MDI); toluene diisocyanate (TDI); chloramine-T (CH); and piperazine (PI)) or contact sensitizers (2,4-dinitrochlorobenzene (DNCB); and oxazolone (OXA)). Non-sensitized mice were treated dermally with solvents and challenged intratracheally with the respective test chemicals as solvent controls. Increases in total serum IgE levels were observed in all treated mice, with apparent differences in cytokine profiles. PA caused statistically significant increases in Th2 cytokines, IL-4, IL-5 and IL-13, compared with the control. IL-5 was also found to be increased with CH. The other three respiratory sensitizers caused statistically significant increases in IL-13. In contrast, no change was apparent with contact sensitizers, DNCB and OXA, in these Th2 cytokines. Increases in the Th2 cytokines indicate that all five respiratory sensitizers induced immune responses in lungs. Interestingly, elevation of G-CSF levels in BALF appeared with all five respiratory sensitizers but not the two contact sensitizers. The findings suggest that G-CSF could be effective to identify respiratory sensitizers in animal models.

Comparison of cytokine profiles in bronchoalveolar lavage fluid of mice exposed to respiratory and contact sensitizers