Quaternary ammonium compounds in hypersensitivity reactions

Abstract

Quaternary ammonium compounds (QAC) are commonly used disinfectants, antiseptics, preservatives, and detergents due to their antibacterial property and represent the first used biocides before phenolic or nitrogen products. Their common structure consists of one or more quaternary ammonium bound with four lateral substituents. Their amphiphilic structure allows them to intercalate into microorganism surfaces which induces an unstable and porous membrane that explains their antimicrobial activity towards bacteria, fungi, and viruses. QAC are thus found in many areas, such as household products, medicines, hygiene products, cosmetics, agriculture, or industrial products but are also used in medical practice as disinfectants and antiseptics and in health care facilities where they are used for cleaning floors and walls. QAC exposure has already been involved in occupational asthma in healthcare workers or professional cleaners by many authors. They also have been suggested to play a role in contact dermatitis (CD) and urticaria in workers using cosmetics such as hairdressers or healthcare workers, inciting reglementary agencies to make recommendations regarding those products. However, distinguishing the irritant or sensitizing properties of chemicals is complex and as a result, the sensitizing property of QAC is still controverted. Moreover, the precise mechanisms underlying the possible sensitization effect are still under investigation, and to date, only a few studies have documented an immunological mechanism. Besides, QAC have been suggested to be responsible for neuromuscular blocking agents (NMBA) sensitization by cross-reactivity. This hypothesis is supported by a higher prevalence of quaternary ammonium (QA)-specific IgE in the professionally exposed populations, such as hairdressers, cleaners, or healthcare workers, suggesting that the sensitization happens with structurally similar compounds present in the environment. This review summarizes the newest knowledge about QAC and their role in hypersensitivities. After describing the different QAC, their structure and use, the most relevant studies about the effects of QAC on the immune system will be reviewed and discussed.

Keywords: adjuvant; antibacterial; disinfectant; hypersensitivity; irritant; quaternary ammonium; sensitization; sensitizer.

FIGURE 1

The general structure of QAC.

FIGURE 2

Putative mechanisms of action of QAC. According to the literature, QAC have been reported in contact dermatitis (A) and in asthma (B). They own irritant properties (A1,B1), but have also been described as sensitizers (A2,B2). Other reports attribute adjuvant effect to QAC (C). (A1) In the irritant induced-contact dermatitis mechanism, QAC alter the skin by the production of ROS and the activation of the AA pathway. (A2) QAC can also activate the immune system in allergic contact dermatitis, by triggering a specific cellular response, with the recruitment of CD4⁺ and CD8⁺ T cells in the skin. ILC2 have also been reported in the pathophysiology and anti-QA specific IgE have also been described in response to QAC applied on the skin. (B1) Asthma symptoms of QAC can be attributed to irritant mechanisms, by the production of ROS, epithelial shedding, cell necrosis, the recruitment of neutrophils and macrophages and the release of proinflammatory cytokines. Direct histamine release has also been described. (B2) Allergic asthma is mediated by a specific immune response, mediated by Th2 lymphocytes, leading to the production of anti-QA specific IgE, the degranulation of mast cells and the recruitment of eosinophils. (C). The adjuvant effect is described as the increase of the allergenicity of other compounds. AA, arachidonic acid; DC, dendritic cell; DLN, draining lymph node; ILC2, type-2 innate lymphoid cells; LB, B lymphocytes; LT, T lymphocytes; QA, quaternary ammonium; QAC, quaternary ammonium compound; ROS, reactive oxygen species; Th, helper T cell; TSLP, thymic stromal lymphopoietin.