Augmented Latex‐Specific IGE Antibody Response in BALB/c Mice Upon Concurrent Exposure to Natural Rubber Latex Proteins with Glutaraldehyde

Abstract

Health care workers are exposed to numerous agents that are known to induce hypersensitivity‐mediated diseases. Yet, little is known regarding the role of coexposure to these agents on the development of hypersensitivity responses. The present studies were conducted to evaluate the immunomodulatory role of dermal exposure to glutaraldehyde (Glut) on the induction of IgE antibodies to natural rubber latex (NRL) proteins. Female BALB/c mice were dermally exposed to Glut (0.05–1 ppm; 0.1–1%) and nonammoniated latex (NAL; 25 µg) 5 days/week for up to 86 days. The NAL alone at concentrations up to 1% did not induce significantly elevated levels of total serum or latex specific IgE. In contrast, both total and NAL‐specific serum IgE were dose‐dependently (p < 0.01 and p < 0.05, respectively) elevated in mice concurrently exposed to 25 µg NAL and increasing concentrations of Glut up to 0.75 ppm. Further testing was performed to investigate the mechanism by which Glut augmented the latex‐specific response. Barrier integrity tests demonstrated that Glut did not induce sufficient disruption of the strateum corneum (less than 1% 3H20 penetration was observed in a guinea pig model) to allow for increased penetration of the latex proteins. However, co‐exposure to 25 µg NAL and 0.75 ppm Glut for 2 days as compared to the vehicle control was shown to induce a 15‐fold increase in MHC II positive Langerhans' cells in the epidermis. Additional experiments confirmed the upregulation of a Th2 response. Upon sacrifice following 86 days of exposure, animals exposed to 25 µg NAL and 0.75 ppm Glut demonstrated a significant increase (p < 0.01) in CD40 + (3.95 ± 0.38 × 106), B220 + (7.67 ± 1.18 × 106), and IgE + B220 + (3.28 ± 0.75 × 106) cells as compared to the vehicle control groups (2.29 ± 0.18 × 106, 3.31 ± 0.18 × 106, and 0.82 ± 0.15 × 106 cells), respectively. These studies demonstrate the potential for mixed exposures in the health care environment to modulate the development of IgE mediated responses to natural rubber latex proteins, underscoring the importance of environmental factors in the development of allergies to foreign antigens.