Immunomodulatory effect of endotoxin on the development of latex allergy.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Female BALB/c mice were exposed to 25 microg 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.


RESULTS
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-gamma 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.


CONCLUSIONS
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.
Howell
Michael D
MD
Agriculture and Immunotoxicology Group, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA.
Tomazic
Vesna J
VJ
Leakakos
Tina
T
Truscott
Wava
W
Meade
B Jean
BJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000280:Administration, Inhalation; D000818:Animals; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D007840:Latex / Q000276:immunology / Q000633:toxicity; D020315:Latex Hypersensitivity / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012408:Rubber / Q000633:toxicity; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004731:Endotoxins; D007840:Latex; D012333:RNA, Messenger; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D012408:Rubber