Immunomodulatory effect of endotoxin on the development of latex allergy

Although numerous studies have been conducted delineating the clinical manifestations of latex allergy and characterizing the protein allergens, little is known regarding the natural history of the disease. These studies were undertaken to investigate the immunomodulatory role of inhaled endotoxin on the development of latex-specific IgE-mediated responses to natural rubber latex (NRL) proteins by using a mouse model. Female BALB/c mice were exposed to 25 μg of NRL proteins with or without increasing concentrations of endotoxin (50-25,000 EU) through the respiratory tract. Serum antibody levels were evaluated biweekly during the study. After sensitization, mice were challenged with methacholine or NRL proteins, and airway hyperreactivity (AHR) was evaluated with whole-body plethysmography. After NRL challenge, lungs were excised for histopathology, and lung-associated lymph nodes were removed for cytokine mRNA evaluation. When compared with mice exposed to latex alone, mice exposed to latex and endotoxin demonstrated up to 50% lower levels of latex-specific IgE and decreased latex-specific AHR and mucin production. Conversely, these same animals demonstrated increased levels of latex-specific serum IgG2a and IgA antibodies and an increase in IFN-γ and IL-12 mRNA levels in the draining lymph node cells. Concurrent exposure to LPS with nonammoniated latex resulted in increased alveolitis and nonspecific AHR on respiratory challenge with methacholine. Coexposure with LPS and allergen decreased latex-specific IgE but augmented nonspecific AHR. These studies demonstrate that endotoxin associated with NRL gloves can modulate the development of allergic responses to NRL proteins.