Cytokine fingerprinting and hazard assessment of chemical respiratory allergy.
Allergic sensitization of the respiratory tract resulting in occupational asthma and other symptoms can be caused by a variety of chemicals and represents an important occupational health problem. Although there is a need to identify and characterize those chemicals that are able to cause respiratory allergy, there are currently no well validated or widely accepted predictive test methods. Some progress has been made with guinea pig assays, but our attention in this laboratory has focused instead on the development of novel approaches based on an understanding of the nature of immune responses induced in mice by chemical allergens. We have shown that whereas contact allergens provoke in mice selective type 1 immune responses, characterized by the secretion by draining lymph node cells (LNC) of high levels of the cytokine interferon gamma (IFN-gamma), chemical respiratory allergens stimulate instead preferential type 2 responses associated with comparatively high levels of interleukins 4 and 10 (IL-4 and IL-10). The divergent immune responses provoked by different classes of chemical allergens, and the phenotypes of selective cytokine secretion that characterize such responses, form the basis of a novel method-cytokine fingerprinting--that permits chemicals that have the potential to cause respiratory allergy to be identified and distinguished from those that are associated primarily with contact sensitization. In this article the immunobiological basis for cytokine fingerprinting is considered and the development, evaluation and practical application of the assay are reviewed.
Dearman
R J
RJ
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. rebecca.dearman@syngenta.com
Kimber
I
I
D000485:Allergens / Q000276:immunology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000032:analysis; D019570:Inhalation Exposure; D051379:Mice; D016273:Occupational Exposure; D012140:Respiratory Tract Diseases / Q000139:chemically induced* / Q000276:immunology; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D007073:Immunoglobulin E