Chronopharmacology of immune-related diseases

Clock genes, circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN), control various circadian rhythms in many biological processes such as physiology and behavior. Clock gene regulates many diseases such as cancer, immunological dysfunction, metabolic syndrome and sleep disorders etc. Chronotherapy is especially relevant, when the risk and/or intensity of the symptoms of disease vary predicably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. Dosing time influences the effectiveness and toxicity of many drugs. The pharmacodynamics of medications as well as pharmacokinetics influences chronopharmacological phenomena. To escape from host immunity in the tumor microenvironment, cancer cells have acquired several pathways. Immune checkpoint therapy targeting programmed death 1 (PD-1) and its ligand (PD-L1) interaction had been approved for the treatment of patients with several types of cancers. Circadian expression of PD-1 is identified on tumor associated macrophages (TAMs), which is rationale for selecting the most appropriate time of day for administration of PD-1/PD-L1 inhibitors. The therapies for chronic kidney disease (CKD) are urgently needed because of a global health problem. The mechanism of the cardiac complications in mice with CKD had been related the GRP68 in circulating monocytes and serum accumulation of retinol. Development of a strategy to suppress retinol accumulation will be useful to prevent the cardiac complications of CKD. Therefore, we introduce an overview of the dosing time-dependent changes in therapeutic outcome and safety of drug for immune-related diseases.