title: TDI inhalation in guinea-pigs involves migration of dendritic cells.
abstract: Toluene diisocyanate (TDI) can cause occupational asthma, but the mechanism underlying sensitization to this chemical compound remains controversial. The present study aims to investigate whether tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) liberated in the lungs after TDI inhalation can contribute to the migration of dendritic cells from respiratory airways towards lung associated lymph nodes for presentation of TDI hapten. Exposure was studied in two modes: (1) acute exposure (experiment no. 1, 2 and 3) where animals were exposed to 2.962, 1.060, and 1.076 ppm TDI for 1, 4, and two periods of 4 h, respectively; (2) subacute exposure (experiment no. 4, 5 and 6) where animals were exposed to 0.066, 0.110, and 0.999 ppm TDI for 48 h for the two lower doses and 5 days for the highest dose. Depending on the modes of exposure, two to four post exposure times were selected. After acute exposure to 2.962 ppm TDI for 1 h, the increase in TNF-alpha and IL-6 levels in bronchoalveolar lavage (BAL) fluid was observed immediately at the end of inhalation exposure, whereas the maximum number of dendritic cells and total cells occurred at post exposure times of 48 h and 5 days, respectively. In two other acute exposures, the peak increases in TNF-alpha, IL-6 and total cell numbers were observed at 48 h post exposure time, whereas the peak increase in dendritic cells occurred at 24 h. After subacute exposure to 48 h TDI, where TDI concentrations were relatively low (0.006 or 0.110 ppm), a parallel increase in TNF-alpha and IL-6 levels, dendritic and total cell numbers were observed at 0 h post exposure time. This phenomenon was also apparent at 24 h post exposure time when the animals had been exposed to 1.999 ppm TDI for 5 days. From these results, we can conclude that dendritic cells could play a key role as antigen presenting cells in the development of TDI-induced respiratory sensitization, and that their migration toward lung-associated lymph nodes is probably conditioned by cytokine release in their micro-environment. Future work must delineate whether TNF-alpha and IL-6 are solely responsible for the migration of dendritic cells after TDI inhalation, for example by using antibodies to neutralize these cytokines.
authors.affiliation: Institut National de Recherche et de Securite, Vandoeuvre, France.
authors.forename: M
authors.initials: M
authors.lastname: Ban
authors.forename: D
authors.initials: D
authors.lastname: Hettich
authors.forename: M
authors.initials: M
authors.lastname: Goutet
authors.forename: P
authors.initials: P
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D019570:Inhalation Exposure; D015850:Interleukin-6 / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014051:Toluene 2,4-Diisocyanate