Antigen-specific stimulation of histamine releasing factors in diisocyanate-induced occupational asthma

Diisocyanate-induced asthma differs from occupational asthma (OA) caused by protein allergens in that specific IgE antibody responses are rarely identified. To investigate the immunopathogenesis of diisocyanate asthma, diisocyanate-exposed workers were evaluated for in vitro production of antigen-specific mononuclear cell-derived histamine releasing factor (HRF). The mean HRF response to diisocyanate-HSA antigens was significantly greater in patients with OA than in diisocyanate-exposed asymptomatic subjects (p < 0.05). No association was found between HRF and diisocyanate-specific antibodies. Analysis of HRF production by subpopulations of peripheral blood mononuclear cells (PBMC) showed that lymphocytes and adherent cells were major sources of both spontaneous and antigen-stimulated HRF. The results suggest that antigen-specific HRF produced by PBMCs are an important biomarker for diisocyanate-induced asthma. This is the first report of hapten-specific stimulation of PBMCs resulting in HRF production.