Midazolam inhibits IgE production in mice via suppression of class switch recombination

Anaphylactic shock is characterized by increased capillary permeability and a decline in blood pressure due to excessive production of IgE. Midazolam (MDZ) is reported to have immunomodulatory properties. However, little is known about the effect of MDZ on the production of IgE antibody. We examined whether MDZ can suppress antigen-specific and total IgE production followed by IgE class switch recombination (CSR). MDZ was administered intraperitoneally to mice prior to ovalbumin (OVA) plus native cholera toxin (nCT) immunization. Serum OVA-specific and total IgE responses, and surface IgE-positive B cells were analyzed by ELISA and flow cytometry. Furthermore, expression levels of CSR-associated molecules such as germ-line transcript ε (εGLT), germ-circle tanscript ε (εCT), AID, and Id2 in the spleen were compared. The levels of interferon-gamma (IFN-γ) and interleukin (IL)-4 mRNA and protein were also examined in the spleen and serum. MDZ significantly suppressed OVA-specific and total IgE levels in plasma and surface IgE-positive B cells in the spleen. Moreover, MDZ-treated mice had significantly reduced levels of εGLT and εCT. Furthermore, although the levels of IFN-γ mRNA and protein were significantly elevated, those of IL-4 were reduced in MDZ-treated mice. Therefore, MDZ may be an important modulator of allergic responses through its ability to downregulate IgE production.