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IDENTIFYING AIRWAY SENSITIZERS: MRNA CYTOKINE PROFILES INDUCED BY VARIOUS ANHYDRIDES
Citation:
Plitnick, L. M., S. E. Loveless, G. S. Ladics, M. P. Holsapple, R J. Smialowicz, M. R. Woolshiser, P. K. Anderson, C. Smith, AND MJK Selgrade. IDENTIFYING AIRWAY SENSITIZERS: MRNA CYTOKINE PROFILES INDUCED BY VARIOUS ANHYDRIDES. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 193:191-201, (2003).
Description:
Abstract:
Exposure to low molecular weight (LMW) chemicals in the workplace has been linked to a variety of respiratory effects. Within the LMW chemicals, one of the major classes involved in these effects are the acid anhydrides. The immunological basis of respiratory hypersensitivity involves CD4+ T cells, and by virtue of their induction of cytokines typical of the CD4+ T helper type 2 (Th2) cells (Interleukin-4 (IL-4, 10 and 13), respiratory sensitizers may be identified and differentiated from contact sensitizers which induce Th1 cytokines (IL-2 and IFN- . This study addressed the utility of the ribonuclease protection assay (RPA) for the identification of respiratory sensitizers. Four acid anhydrides with known respiratory sensitization potential, trimellitic anhydride (TMA), maleic anhydride (MA), phthalic anhydride (PA) and hexahydrophthalic anhydride (HHPA) were tested. Although previously determined to induce immunologically equivalent responses in a local lymph node assay (LLNA), the initial dose chosen (2.5%) failed to induce Th2 cytokine mRNA expression. To determine if the lack of cytokine expression was related to dose, LLNAs were conducted to develop dose response curves for each of the anhydrides. The highest doses evaluated (4-6-fold higher than those used in the initial RPA) gave equivalent proliferative responses for the various anhydrides and were used for subsequent RPA testing. At these higher doses, significant increases in Th2 cytokine mRNA were observed for all anhydrides tested. These results suggest that the RPA has the potential to serve as a screen for the detection of LMW airway sensitizing chemicals. However, the basis for selecting immunologically equivalent doses may require some modification.