OBJECTIVETributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro.

METHODSWe examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.

RESULTSThe mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.

CONCLUSIONSThe increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.

OBJECTIVESCytokines are critical regulatory molecules that circulate in blood at measurable levels. However, the epidemiology of serum cytokine levels in healthy populations is still limited, particularly for Japanese populations. The objective of this study was to examine the relation between serum cytokine levels and common laboratory tests in a healthy Japanese population.

METHODSWe studied serum levels of six cytokines (interleukin-4 (IL-4), IL-5, IL-6, IL-10, interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF)) in a healthy Japanese population using a sensitive chemiluminescence ELISA (CL-ELISA). We examined the relations between serum cytokine levels and common laboratory tests using multiple regression analysis. We were particularly interested in potential relations between serum cytokine levels and C-reactive protein (CRP) in light of its relation to the risk of cardiovascular events. We also investigated the relation between cytokine levels, alcohol consumption and smoking.

RESULTSAfter adjusting for the influence of other cytokines and laboratory tests, the serum level of IL-4 was associated with IL-5 and GM-CSF. In addition to IL-4, IL-5 was also associated with IL-10 and IFN-γ. IL-6 was associated with IL-10 and IFN-γ, and IL-10 and IFN-γ were associated with GM-CSF. CRP was significantly negatively associated with serum IL-4 level. IL-6 was weakly correlated with alcohol consumption level in this population. IL-5 among smokers tended to be lower than that among nonsmokers.

CONCLUSIONSClose relations among serum cytokine levels were observed in a healthy population. It is interesting that the level of IL-4, an anti-inflammatory cytokine, was inversely related to CRP level, suggested to be a marker of inflammation.

Background/Aims: Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation. Methods: The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. AfterYKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase(p-ERK) 1/2 in the spinal cord was performed. Results: YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord.In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility. Conclusions YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract.This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.