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CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS
Citation:
Plitnick, L. M., S. E. Loveless, G. S. Ladics, M. P. Holsapple, MJK Selgrade, D M. Sailstad, AND R J. Smialowicz. CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. LM Plitnick1, SE Loveless2, GS Ladics2, MP Holsapple3, MJ Selgrade4, DM Sailstad4 & RJ Smialowicz4. 1UNC, Chapel Hill, NC; 2DuPont Co., Haskell Laboratory, Newark, DE; 3Dow Chemical, Midland, MI & 4USEPA, NHEERL, RTP, NC.
Exposure to chemicals in either domestic or occupational settings may result in airway hypersensitivity (AHS). Because cytokines generated during a T cell response are indicative of AHS (Th2) or contact hypersensitivity (CHS) (Th1), cytokine expression in draining lymph nodes (LN) has been used to identify chemicals with AHS potential. In this study, female BALB/c mice were dermally sensitized and challenged with the known respiratory sensitizers trimellitic anhydride (TMA), toluene diisocyanate (TDI) and diphenylmethane-4,4'-diisocyanate (MDI) or the contact sensitizer dinitrochlorobenzene (DNCB). In addition, the respiratory sensitizing potential of dicyclohexylmethane-4,4'-diisocyanate (HMDI) and isophorone diisocyanate (IPDI) was evaluated. Chemical concentrations were varied individually during either sensitization or challenge, or both simultaneously. At various times following challenge, total mRNA was isolated from LN and analyzed by ribonuclease protection assay (RPA). All isocyanates tested, including HMDI and IPDI, induced Th2 cytokines (IL4, IL10 and IL13), supporting reports that the latter are in fact respiratory sensitizers. When concentration was varied during sensitization only, TMA induced higher levels of IL4, IL10 and IL13 than DNCB but not in a dose-dependent manner. Variation of TMA dose during sensitization and challenge similarly induced Th2 cytokines, again with no concentration dependency. Concentration appeared to be a factor only when TMA was varied during challenge alone. Thus, concentration appears not to affect quantitative differences in Th2 responses between TMA and DNCB. An IFNg response to DNCB was not observed, and may be due to the Th2-prone nature of the BALB/c mouse. (This abstract does not reflect EPA policy)
In part, by The Dow Chemical Co. & DuPont Co.