Divergent immunological responses following glutaraldehyde exposure.
Although Glutaraldehyde (Glut) has been demonstrated to be a moderate contact sensitizer, numerous cases of occupational asthma related to Glut exposure have been reported. The purpose of these studies was to examine the dose-response relationship between Glut exposure and the development of T cell-mediated vs. IgE- mediated responses. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.75% to 2.5%. A concentration-dependent increase in lymphocyte proliferation was observed with EC3 values of 0.072% and 0.089% in CBA and BALB/c mice, respectively. The mouse ear swelling test (MEST) was used to evaluate the potential for Glut to elicit IgE (1/2 h post challenge) and contact hypersensitivity (24 and 48 h post challenge) responses. An immediate response was observed in animals induced and challenged with 2.5% Glut, whereas animals induced with 0.1% or 0.75% and challenged with 2.5% exhibited a delayed response 48 h post challenge. IgE-inducing potential was evaluated by phenotypic analysis of draining lymph node cells and measurement of total serum IgE levels. Only the 2.5% exposed group demonstrated a significant increase (P < 0.01) in the percentage of IgE(+)B220(+) cells and serum IgE. Following 3 days of dermal exposure, a significant increase in IL-4 mRNA in the draining lymph nodes was observed only in the 2.5% exposed group. These results indicate that the development of an immediate vs. a delayed hypersensitivity response following dermal exposure to Glut is at least in part mediated by the exposure concentration.
Azadi
Shahla
S
National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. sazadi@cdc.gov
Klink
Kimberly J
KJ
Meade
B Jean
BJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000473:pathology; D004487:Edema / Q000473:pathology; D005260:Female; D005976:Glutaral / Q000633:toxicity*; D007073:Immunoglobulin E / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D005976:Glutaral