Inflammatogenic and adjuvant properties of HEMA in mice

2-Hydroxyethylmethacrylate (HEMA), a common constituent in dental materials, is known to cause hypersensitivity reactions. While the means by which this small molecule causes adverse responses has not been ascertained, we have previously demonstrated that it binds to protein and in mice induces the production of autoantibodies to HEMA-conjugated self-protein. The present study explores the inflammatory and adjuvant properties of HEMA in response to the subcutaneous injection of HEMA and a protein. Ovalbumin (OVA) was used as a 'reporter antigen', and mouse serum albumin (MSA), conjugated in vitro with HEMA (MSA(H)) to a low degree (0.5 molecules of HEMA per molecule of MSA on average), was used to mimic a possible in vivo situation. Inflammatory responses at injection sites were scored by using an ordinal scale, and immunoglobulin (Ig)G1, IgG2a, and IgE activities to OVA or MSA were assessed by enzyme-linked immunosorbent assay (ELISA). Injections of 20 micromol HEMA induced overt inflammatory skin responses, the severity of which was influenced by the co-administered substances. A significantly higher IgG1 and IgE response to OVA was induced by the presence of HEMA. Interestingly, injections with low conjugated MSA(H) only induced the production of autoantibodies if free HEMA was included at the time of immunization. These findings suggest that HEMA is an inflammatogenic substance with adjuvant properties.