We investigated the effect of interleukin-6 (IL-6) expression on sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels in cultured rat neonatal ventricular myocytes. IL-6 plays a key role in regulating cardiac hypertrophy and the development of heart failure, and SERCA, ANP and BNP are all cardiac hormones with regulatory properties. Compared with baseline measurements, treatment with 50 U/ml IL-6 significantly decreased SERCA gene expression, but significantly increased ANP and BNP gene expression in the cardiac myocytes. These results suggest that the clinical overproduction of IL-6 in response to infection, autoimmune disease and cancer might be responsible for cardiac hypertrophy. Cardiac hypertrophy may result from the imbalance of both natriuretic peptides and SERCA transciption levels, caused by elevated IL-6 expression.

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

No abstract

This study determined the presence of adiponectin, T-cadherin (an adiponectin receptor) and tumour necrosis factor-a (TNF-a) in damaged myocytes from autopsied patients with acute or old myocardial infarction (MI) or dilated cardiomyopathy (DCM), using immunohistochemical staining. The enrolled patients included eight with acute MI, six with old MI and seven with DCM. Four autopsied individuals with no cardiac lesions were also enrolled as controls. Adiponectin and TNF-a were not observed in normal myocytes from control subjects, but T-cadherin was weakly detected. Immunoreactivity for adiponectin and T-cadherin was observed at the periphery of damaged myocytes from MI and DCM patients; intracellular reactivity for TNF-a was also seen. There were no statistically significant differences in the degree of reactivity for each molecule in the myocytes between the MI and DCM patients. These results suggest that the presence of adiponectin and TNF-a in damaged myocytes may contribute to the processes of myocardial injury occurring in MI and DCM.

SUMMARYA mouse model of encephalomyocarditis (EMC) virus-induced myocarditis was used to investigate the expression of adiponectin in damaged cardiomyocytes. We intraperitoneally injected EMC virus into leptin-deficient ob/ob (OB) mice and wild-type (WT) mice. OB mice were divided into two subgroups consisting of mice with no intervention and mice receiving leptin replacement starting simultaneously with viral inoculation. We determined differences in heart weight, cardiac histological score, numbers of infiltrating and apoptotic cells in the myocardium, expression levels of adiponectin and TNF-α mRNA in the heart, adiponectin immunoreactivity in myocytes, adiponectin and TNF-α concentrations in the heart, and immunoreactivity of adiponectin receptors in myocytes between OB mice and WT mice. There was significantly decreased adiponectin mRNA expression, immunoreactivity, and protein level in the heart, and reduced immunoreactivity of adiponectin receptor 1 in myocytes from OB mice on days 4 and 8 after viral inoculation as compared with those in WT mice, together with increased cardiac weight, severe inflammatory myocardial damage, and increased levels of cardiac TNF-α mRNA and protein. Replacement of leptin in OB mice inhibited the development of severe myocarditis through augmentation of adiponectin mRNA, immunoreactivity, and protein level, increased adiponectin receptor 1 immunoreactivity in myocytes, and suppressed levels of TNF-α mRNA and protein. These results suggest that impaired expression of cardiac adiponectin may contribute to the progression of viral myocarditis through enhanced expression of TNF-α under a leptin-deficient condition. (Int Heart J 2006; 47: 107-123) Key words: Adiponectin, Leptin deficiency, Viral myocarditis, Cardiomyocyte HEART failure is generally considered to begin with myocyte damage caused by a variety of pathological conditions that include ischemia, toxins, and myocardial infection. The heart compensates by dilatation and cellular hypertrophy, and eventually decompensates, resulting in heart failure. A proinflammatory cytokFrom the