Immunomodulatory roles of endotoxin and glutaraldehyde in the development of latex allergy

Abstract

Although much data has been obtained related to the clinical manifestations of latex allergy and the characterization of the protein allergens, little is known regarding the natural history of the disease. These studies were undertaken to demonstrate the immunological relevance of both dermal and respiratory exposure in the development of latex allergy and to investigate the role of co-exposure by these routes to other agents in the health care environment on the development of NRL sensitization. An initial study in female BALB/c mice demonstrated comparable rates of induction of latex specific IgE following dermal and respiratory latex exposure, demonstrating the importance of both routes in the development of latex allergy. Upon further investigation using whole body plethysmography, non-specific airway hyperreactivity to methacholine was observed in mice following both dermal and intratracheal sensitization with latex proteins. In contrast, at these exposure levels latex specific airway hyper-reactivity was only observed in dermally sensitized mice. Endotoxin, a common contaminant of powdered gloves, and glutaraldehyde, a frequently used cold sterilant, were chosen to investigate the immunomodulatory effects of other agents in the health care setting on the development of latex allergy. In comparison with mice exposed to latex alone, mice concurrently exposed to latex and increasing concentrations of endotoxin demonstrated ~50% lower levels of latex specific IgE and a decrease in latex specific airway hyper-reactivity and mucin production. The same animals demonstrated increased levels of latex specific IgG2a and IgA, cellular infiltration (i.e. macrophages and neutrophils) into the peribronchial and perivascular regions of the lung, messenger IFN-γ and IL-12 levels in the draining mediastinal lymph nodes, and non-specific airway hyper-reactivity upon respiratory challenge with methacholine. Upon concurrent dermal exposure to latex and concentrations of glutaraldehyde surrounding the permissible exposure limit, mice demonstrated a dose responsive increase in latex specific IgE levels through an as yet undetermined mechanism. These studies demonstrate the potential for mixed exposures in the health care environment to diversely modulate the development of IgE mediated responses to NRL proteins underscoring the importance of environmental factors in the development of allergies to foreign antigens. iii ACKNOWLEDGEMENTS To my advisor, mentor and friend, Dr. Barbara Jean Meade, for her knowledge, support, discipline, motivation and persistence in helping me grow as a scientist. To Dr. Albert E. Munson for always stimulating the mind to understand both the question and answer in all of science and life. To Drs. Christopher Cuff, Daniel Lewis, and Rosana Schafer for supporting me through out the course of my training and offering valuable insight into my research. To my predecessors, Drs. Michael Woolhiser, Scott Manetz, and Ben Hayes, for their direction, assistance, patience and advice during my early years in the...