Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide

Abstract

Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625-2%), evaluated by ear swelling in female BALB/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. Phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4 T-cells, CD8 T-cells, and dendritic cells in the draining lymph nodes (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4 T-cell and CD8 T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.

Topical Application of the Quaternary Ammonium Compound Didecyldimethylammonium Chloride Activates Type 2 Innate Lymphoid Cells and Initiates a Mixed-Type Allergic Response

“…To further evaluate type of hypersensitivity response induced by DDAC, IgE was evaluated following dermal exposure. Since we previously identified that exposure duration may influence the development of allergic responses (Shane et al ., 2017), IgE levels in mice exposed to DDAC for 14-days were assessed at 28 days post initial exposure. Mice (n=5) were treated for 14-days with DDAC and rested for 14-days.…”

“…To quantify serum IgE levels a standard colorimetric sandwich ELISA was performed according to manufacturer directions (Mouse IgE Ready-Set-Go!, eBioscience). To determine local production of IgE the IgE + B220 + (IgE + B-cells) population were analyzed by flow cytometry as previously described using IgE-FITC (R35–72) (BD Biosciences) (Shane et al ., 2017).…”

“…Recently our laboratory determined that another QAC, didecyldimethylammonium bromide (DDAB), elicits multiple types of hypersensitivity reactions following topical application (Shane et al ., 2017). Phenotypic analyses revealed significant increases in the number of immune cells in the draining lymph nodes (DLN) following 4 and 14 days of exposure with increased activation of CD4+ and CD8+ T-cells at 4-days, and elevated IgE levels only at 14 days post exposure.…”

Novel cutaneous mediators of chemical allergy

“…Additionally, properties of chemical allergens and commensal bacteria add to the complex landscape of skin immunity. Many chemical sensitizers are also anti-microbial agents (Anderson et al 2010Shane et al 2017). While these agents may be beneficial in protecting against pathogenic bacteria, the influence of exposure on resident bacterial populations warrants further investigations.…”

Quaternary Ammonium Compound Disinfectants Reduce Lupus-Associated Splenomegaly by Targeting Neutrophil Migration and T-Cell Fate

“…Quaternary ammonium compounds (QACs) are ubiquitous biocides (15), antiseptics (16), and widely used surface disinfectants (16). Exposure to QACs is associated with development of topical hypersensitivity (17) and asthma (18) especially in hospital settings (19). Although the exact mechanisms of how QACs modulate immune cell responses are unclear, QAC-induced allergic responses have been attributed to abrogated type 2 innate lymphoid cell responses (20).…”