CHARACTERIZATION OF HISTAMINE-RELEASING FACTORS IN DIISOCYANATE-INDUCED OCCUPATIONAL ASTHMA

Immunologic mechanisms contributing to diisocyanate-induced occupation al asthma (OA)are poorly defined. There is a relatively low incidence of diisocyanate-specific IgE antibody responses. The frequent occurren ce of delayed onset asthmatic responses in workers with diisocyanate a sthma suggests a role for cellular immune mechanisms. We have shown in vitro production of antigen-specific mononuclear cell-derived histami ne releasing factors (HRF) by peripheral blood mononuclear cells (PBMC s) of workers with OA. Monocyte chemoattractant protein-1 (MCP-1) and RANTES (acronym for ''regulated on activation,normal T expressed and s ecreted'') are chemokines found in PBMC supernatants that express HRF activity. Diisocyanate-exposed workers were tested for diisocyanate an tigen-stimulated enhancement of HRF, MCP-I, and RANTES production in s upernatants of PBMCs and for serum specific IgE and IgG antibody level s to diisocyanate antigens bound to human serum albumin (HSA). PBMCs o f workers with diisocyanate OA showed significantly increased producti on of antigen-specific HRF activity and MCP-1 (>300 ng/ml) compared to diisocyanate-exposed asymptomatic workers (P < 0.05). Antigen-stimula ted enhancement of MCP-I mRNA was demonstrated by reverse-transcriptio n PCR. RANTES mRNA and chemokine secretion (<1 ng/ml) was also demonst rated in PBMCs, but did not show antigen enhancement in OA workers. Ha pten specificity for the diisocyanate chemical to which a patient had been exposed was demonstrated for HRF enhancement and for IgG antibody reactions, but not for IgE reactions. HRF production was demonstrated in PBMC subpopulations, including lymphocytes and purified T cells. O A subjects showed increased CD8(+) cells by immunofluorescence (mean C D4(+):CD8(+) = 1.2 +/- 0.2). The results suggest that diisocyanate ant igen enhancement of HRF and MCP-I production are stimulated by hapten- specific T cell reactions. Since a weak association has been found bet ween IgE antibody synthesis and induction of diisocyanate OA, the role of T cell cytokines and chemokines in the pathogenesis of OA requires further investigation.