Immunomodulatory properties of cimetidine: Its therapeutic potentials for treatment of immune-related diseases

Histamine exerts potent modulatory impacts on the cells of innate- [including neutrophils, monocytes, macrophages, dendritic cells (DCs), natural killer (NK) cells and NKT cells] and adaptive immunity (such as Th1-, Th2-, Th17-, regulatory T-, CD8+ cytotoxic T cells, and B cells) through binding to histamine receptor 2 (H2R). Cimetidine, as an H2R antagonist, reverses the histamine-mediated immunosuppression, as it has powerful stimulatory effects on the effector functions of neutrophils, monocytes, macrophages, DCs, NK cells, NKT cells, Th1-, Th2-, Th17-, and CD8+ cytotoxic T cells. However, cimetidine reduces the regulatory/suppressor T cell-mediated immunosuppression. Experimentally, cimetidine potentiate some immunologic activities in vitro and in vivo. The therapeutic potentials of cimetidine as an immunomodulatory agent were also investigated in a number of human diseases (such as cancers, viral warts, allergic disorders, burn, and bone resorption) and vaccination. This review aimed to provide a concise summary regarding the impacts of cimetidine on the immune system and highlight the cellular mechanisms of action and the immunomodulatory effects of this drug in various diseases to give novel insights regarding the therapeutic potentials of this drug for treatment of immune-related disorders. The review encourages more investigations to consider the immunomodulatory characteristic of cimetidine for managing of immune-related disorders.