Divergent immunological responses following glutaraldehyde exposure.
Azadi-S; Butterworth-LF; Meade-BJ
Toxicologist 2002 Mar; 66(1-S):79
Glutaraldehyde (Glut) is a potent contact sensitizer, additionally numerous cases of occupational asthma related to Glut exposure have been reported in recent years. The purpose of this study was to examine the Dose-Response relationship between Glut exposure and the development of Th1 vs. Th2 responses using a murine model. Initial evaluation of the sensitization potential was conducted using the standard Local Lymph Node Assay in CBA mice. Female BALB/c mice (N-5-8 per group) were used for all other studies. The IgE inducing potential was evaluated by phenotypic analysis of IgE+B220+ cells in lymph nodes draining the site of topical exposure and measurement of total serum IgE levels. The Mouse Ear Swelling Test (MEST) was used to evaluate the potential of Glut to elicit urticaria (30 min post challenge) and contact hypersensitivity (24 and 48 hrs post challenge). A dose dependent increase in lymphocyte proliferation as measured by 3H-thymidine incorporation and the %B220+ cells was observed following exposure to 0.1, 0.75, and 2.5% Glut with a positive response (SI>3 in LLNA) being observed at all concentrations tested. The MEST demonstrated an immediate response (Th2) in animals induced and challenged with 2.5% Glut, whereas animals induced with 0.1 or 0.75% and challenged with 2.5% exhibited a delayed response (Th1) at 48 hrs. post challenge. In agreement with the MEST results, only the 2.5% dose group had a significant increase (p<0.01) in serum IgE levels and % IgE+B220+ draining lymph nodes cells. The results of these studies indicate that the induction of a Th1 vs. Th2 response following dermal exposure to Glut is at least in part mediated by the exposure concentration. These studies were supported in part by NIEHS intra-agency agreement #Y1-ES-0001-01.
Animal-studies; Immune-reaction; Bronchial-asthma; Sensitivity-testing; Dose-response; Lymph-nodes; Laboratory-animals; Respiratory-system-disorders; Pulmonary-system-disorders
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee