Animal models are frequently used to conduct mechanistic studies that due to test article toxicity or sensitization potential would be unethical to perform in humans. Several laboratories have developed models to study latex allergy and although these include rabbit and guinea pig models, most animal research has been conducted in murine models. Although clinical and exposure data have been gathered on the factors affecting the elicitation of responses in latex allergic individuals, less is known regarding the development of sensitization. Coupled with in vitro dermal penetration studies, murine models were established to investigate the role of the route of exposure in the development of latex sensitization. Time course and dose response studies have shown multiple subcutaneous (s.c.) administrations of as little as 0.19 ug non-ammoniated latex proteins (NAL) elicited IgE production in 5 weeks. Animals exposed s.c., intratracheally (i.t.) or topically to 12.5 ug NAL demonstrated IgE production within 2, 3 and 5 weeks, respectively. Although elevations in total latex specific IgE have been observed following topical, intranasal (i.n.), i.t. and s.c. exposures, pulmonary responses (as measured by plethysmography) following respiratory challenge was only seen in mice sensitized by the topical or respiratory routes. Both in vitro penetration and in vivo studies highlight the importance of skin condition in the development of latex allergy with enhanced penetration and earlier onset of IgE production seen with experimentally abraded skin. These models are also being used to investigate the role of concurrent exposure to other chemicals and agents in the workplace on the development of latex allergy. I.n. co-exposure to endotoxin with recombinant Hev b 5 was reported to increase the Hev b 5 specific IgE response without altering total IgE. In our model, i.n. co-exposure of endotoxin with a mixture of NAL proteins was found to suppress the elevation in total IgE seen in response to NAL alone. These observations underscore the complexity of the mechanisms involved in the development of an allergic response to a complex mixture.
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania