Circadian rhythm affects the magnitude of contact hypersensitivity response in mice

Background The circadian rhythm controls multiple biological processes, including immune responses; however, its impact on cutaneous adaptive immune response remains unclear. Methods We used a well-established cutaneous type IV allergy model, contact hypersensitivity (CHS). We induced CHS using dinitrofluorobenzene (DNFB). Mice were sensitized and elicited with DNFB in the daytime or at night. Results In mice, a nocturnally active animal, we found that ear swelling increased when mice were sensitized at night compared with in the daytime. In addition, cell proliferation and cytokine production in the draining lymph nodes (LNs) were promoted when sensitized at night. We hypothesized that these differences were due to the oscillation of leukocyte distribution in the body through the circadian production of adrenergic hormones. Administration of a beta 2-adrenergic receptor (beta 2AR) agonist salbutamol in the daytime decreased the number of immune cells in blood and increased the number of immune cells in LNs. In contrast, a beta 2AR antagonist ICI18551 administration at night increased the number of immune cells in blood and decreased the number of immune cells in LNs. Accordingly, the severity of CHS response was exacerbated by salbutamol administration in the daytime and attenuated by ICI18551 administration at night. Conclusion Our study demonstrated that the magnitude of adaptive CHS response depends on the circadian rhythm and this knowledge may improve the management of allergic contact dermatitis (ACD) in humans.