Natural killer cell function changes by the Japanese Kampo Medicine Juzentaihoto in General fatigue patients

Abstract

BackgroundPhysical/mental fatigue can alter behavior and reduce cognitive abilities. Even in healthy people, general fatigue correlates with NK cell function. Juzentaihoto (JTT) is a popular Kampo medicine used to treat general fatigue. In many animal models, JTT enhances immune functions, such as cytotoxic T-lymphocyte and NK cell activities. This is the first clinical study has examined the effect of JTT in patients with general fatigue. PurposeWe investigated whether peripheral NK cell populations and functions are altered by JTT treatment in patients with general fatigue. Patients and MethodsThe open-label unblinded study included ten patients (two males, eight females; median age 36.5 years, range 29–46 years) with general fatigue (Performance Status, PS 0–2) and. As controls, six healthy volunteers (two males, four females; median age [range]: 39 [36–45] years) were also enrolled in this study and provided informed consent before sampling. All patients were administered JTT three times per day before each meal for 28 consecutive days and were evaluated twice weekly for 42 days to assess compliance and adverse events. The primary endpoint was fatigue score obtained by a subjective numerical rating scale and PS. The secondary endpoint was the effects of JTT on circulating lymphocytes based on the expression of surface receptors in specific lymphocytic subsets. ResultsExpression of activation markers significantly increased from day 0–28 and decreased after 42 days. Inhibitory markers were upregulated in the cluster of high cytokine-producing ability but were downregulated in the fraction with high cytotoxicity. Increased expression of functional markers was observed following interleukin-2 stimulation in vitro. ConclusionsJTT induces cytotoxic activity of NK cells in patients with general fatigue. NK cells may maintain a balanced state by increasing inhibitory functions. Oral administration of JTT may improve immune function by activating NK cells.