title: Dynamics in cytokine responses during the development of occupational sensitization to rats.
abstract: BACKGROUND
  Occupational allergy forms an attractive model to study the development of allergic responses, as in some occupations it has a high incidence and develops quickly. In a cohort of starting laboratory animal workers, we previously found 20% sensitization to animal allergens within 2 years.
  
  
  METHODS
  We compared cellular responses of incident laboratory animal workers who developed rat-specific sensitization (cases, n = 18) during 2 years of follow-up to control animal workers matched for atopic status but without sensitization after follow-up (controls, n = 18). Practically, this is a case-control study, nested within the cohort. Rat-specific IgE antibodies were measured in sera, and allergen-specific and nonspecific cytokine responses were measured in whole blood and in isolated peripheral blood mononuclear cells.
  
  
  RESULTS
  Self-reported allergic symptoms were related to the presence of rat-specific IgE (P ≤ 0.01). Cases developed a rat allergen-specific interleukin (IL)-4 response during sensitization, while controls did not show an increased IL-4 response (at visit D: 33 vs 5 IL-4 producing cells/10(6) cells, P < 0.001). The IL-4 response was related to the levels of rat-specific IgE in cases (visit D: rho = 0.706, P < 0.001). By contrast, allergen-specific IL-10 and interferon γ (IFNγ) responses as well as nonspecific cytokine responses were comparable between cases and controls.
  
  
  CONCLUSIONS
  This study is the first to show the development of an allergen-specific IL-4 response in adult human subjects during allergen-specific sensitization. This IL-4 response was quantitatively associated with the development of the specific IgE antibodies. Allergen-specific or nonspecific IL-10 and IFNγ responses showed no protective effect on the development of allergic sensitization.
authors.affiliation: Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. e.j.m.krop@uu.nl
authors.forename: Esmeralda J M
authors.initials: EJ
authors.lastname: Krop
authors.forename: M A
authors.initials: MA
authors.lastname: van de Pol
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.forename: D J J
authors.initials: DJ
authors.lastname: Heederik
authors.forename: R C
authors.initials: RC
authors.lastname: Aalberse
authors.forename: J S
authors.initials: JS
authors.lastname: van der Zee
mesh_terms: D017750:Animal Technicians; D000818:Animals; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology*; D017056:Medical Laboratory Personnel; D009784:Occupational Diseases / Q000209:etiology / Q000276:immunology*; D016273:Occupational Exposure / Q000009:adverse effects; D051381:Rats / Q000276:immunology*
chemical_list: D016207:Cytokines; D015847:Interleukin-4; D007073:Immunoglobulin E