Dental acrylates and methacrylates - Interactions with the immune system

Sammanfattning: Professionals working in dentistry have reported adverse effects, such as allergic contact dermatitis due to exposure to different methacrylates/acrylates. Leakage of such monomers from dental fillings due to incomplete curing is also common. Monomers are released into the oral cavity and some may also diffuse through the dentin and reach the dental pulp. In the tissue, monomers will come in contact with different cells of the immune system. At present, there is a lack of knowledge of the effects these monomers might have on cells. The main objective of this thesis was to investigate possible effects of four different methacrylate/acrylate monomers on the immune system in vivo and in vitro. The studied methacrylates and acrylate were ethyl methacrylate (EMA), diethylene glycol diacrylate (DEGDA), 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA). In summary, our in vivo and in vitro results showed that: • HEMA affects the immune system by inducing formation of the NLRP3 inflammasome (Study I). • TEGDMA has adjuvant properties and the ability to modulate cytokine production from peripheral blood mononuclear cells, which may lead to interference with the normal immune response to various agents, self or non-self, present in the pulp and the oral mucosa (Study II). • HEMA acts as a mucosal adjuvant when applied sublingually together with ovalbumin (OVA) or Streptococcus mutans in mice (Study III). • The different monomers affect the production, increase as well as decrease, of various cytokines in vitro by peripheral blood mononuclear cells. Antibody production and T cell activity to OVA was increased in mice immunized with OVA in combination with methacrylates (Study IV). Bacteria and bacterial products such as hydrogen sulfide (H2S) challenge the oral mucosa. We wanted to investigate whether H2S also affects the immune system in similar way as HEMA, i.e., induce formation of the NLRP3 inflammasome. • Human mononuclear leukocytes exposed to H2S had an enhanced production of NLRP3 inflammasome- dependent secretion of IL-1β and IL-18. (Study V). Thus, this may be a mode for H2S to contribute to the inflammatory host response and pathogenesis of periodontal disease In summary, the different methacrylate/acrylate monomers frequently used in dental restoration materials may interfere with the immune system in many different ways. The increase as well as the decrease in cytokine production from human mononuclear cells is affected by all these methacryleate/acrylate monomers. The T and B cell activity is also affected by all tested methacrylates . Thus, this may be a model that provide some insight into the nature of the immune responses to methacrylates and acrylates, and may advance the development of more biocompatible restorative materials in the future for clinical use.