Proinflammatory and regulatory mechanisms in allergic contact dermatitis caused by methylchloroisothiazolinone and methylisothiazolinone.

BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the cause of an increasing number of contact allergies. Understanding the mechanisms by which MCI/MI induces proinflammatory and regulatory factors production is necessary to understand the outcome of allergic contact dermatitis (ACD).

OBJECTIVES: To evaluate the dysfunction of proinflammatory cytokines and regulatory factors in the positive MCI/MI patch test at the transcriptional and protein expression levels. Moreover, to analyse the cytokines production induced by MI in peripheral blood mononuclear cells (PBMCs).

MATERIALS AND METHODS: The selected patients had positive MCI/MI patch test results. The expression of proinflammatory factors was evaluated by q-PCR and immunochemistry at 48 hours of positive MCI/MI patch test. The MCI/MI- or MI- induced secretion of IL-1β, TNF and IL-6 by PBMC was analysed by flow cytometry.

RESULTS: The results showed a decreased TLR4 expression with upregulated IL6, FOXP3, IL10 and TGFβ mRNA expression as assessed by q-PCR at the site of the MCI/MI skin reaction. We detected increased protein levels of TLR4, FOXP3 and IL-10 in the dermis layer in the ACD reaction by immunocitochemistry. Moreover, MCI/MI induced proinflammatory cytokine production by PBMC through the NF-κB signalling pathway.

CONCLUSION: Considering the altered innate immune response triggered by MCI/MI sensitization, these findings indicate that the regulatory process at the induction phase of ACD is a crucial mechanism. Given the increase in occupational and domestic exposure to MCI/MI, the underlying immunological mechanisms should be understood.