title: Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individuals.
abstract: BACKGROUND
  Delayed-type hypersensitivity reactions to nickel (Ni2+) in humans are associated with increased production of both T helper (Th) 1- and Th2-like cytokines. Cytokine responses to the major group of contact allergens, i.e. organic compounds, have been less extensively studied. We have investigated here the cytokine production induced by a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), the active ingredients in common preservatives that are capable of eliciting allergic contact dermatitis.
  
  
  OBJECTIVE
  To characterize the immune response induced by MCI/MI in terms of the production of Th1- and Th2-like cytokines in peripheral blood mononuclear cells (PBMC) from allergic and non-allergic subjects.
  
  
  METHODS
  Ten subjects with a history of contact allergy to MCI/MI and nine age-matched non-allergic volunteers participated. Their actual status was confirmed by patch testing. PBMC were cultured in the presence or absence of MCI/MI; cell proliferation was measured employing [3H]thymidine incorporation; and the number of cytokine-producing cells was determined using the enzyme-linked immunospot (ELISpot) assay and the levels of soluble cytokines in culture media by the enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The proliferative response of PBMC to MCI/MI was significantly greater in the case of the allergic group than for the non-allergic group, as was the production of interleukin (IL)-2 and IL-13 (as determined by ELISpot and/or ELISA). PBMC from three of the allergic individuals with increased production of IL-2 and IL-13 responded to MCI/MI with elevated numbers of cells producing IL-4 and IL-5. The increases in the production of IL-2, IL-4, IL-5 and IL-13 were positively correlated.
  
  
  CONCLUSIONS
  MCI/MI elicited concomitant production of both Th1- and Th2-like cytokines by PBMC from subjects with contact allergy to these substances. This finding indicates that the organic compounds MCI/MI elicit a mixed Th1- and Th2-type of response, similar to that elicited by the metal ion Ni2+ in Ni2+-sensitized individuals.
authors.affiliation: Department of Medicine, Unit of Clinical Allergy Research, Karolinska Institutet and Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Masjedi
authors.forename: N
authors.initials: N
authors.lastname: Ahlborg
authors.forename: B
authors.initials: B
authors.lastname: Gruvberger
authors.forename: M
authors.initials: M
authors.lastname: Bruze
authors.forename: A-T
authors.initials: AT
authors.lastname: Karlberg
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000276:immunology*; D010328:Patch Tests; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013844:Thiazoles / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000485:Allergens; D016207:Cytokines; D007378:Interleukins; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma