Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individuals

Abstract

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. 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. 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). 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. 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.