In this study, we first measured some
cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the
cytokines measured
interleukin (IL) -18 was the most prominently up-regulated
cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in
mice,
focusing especially on
natural killer T (NKT) cell induction.
Mice fed JTT were compared to control group ones. After sacrifice, the
liver was fixed, embedded and stained.
Transmission electron microscope (TEM) observations were performed. Although the
mice receiving the
herbal medicine had same appearance, their
livers were
infiltrated with massive
mononuclear cells, some of which were aggregated to form clusters.
Immunohistochemical staining revealed that there was abundant
cytokine expression of IL-12 and IL-18 in the
liver of JTT treated
mice. To clarify what the key molecules that induce
immunological restoration with JTT might be, we next examined in vitro
lymphocyte cultures.
Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of
interferon (
IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their
activation, following
immunological restoration could contribute to
anti-tumor effects.
