The significance of T cells, B cells, antibodies and macrophages against encephalomyocarditis (EMC)-D virus-induced diabetes in mice.

In order to clarify the significance of protective mechanisms against encephalomyocarditis (EMC) virus-induced diabetes in mice, we studied the relative importance of T cells, B cells, antibodies and macrophages in the prevention of virus-induced diabetes. Neither T cell-deficient athymic nude mice nor B cell-deficient microMT/microMT mice showed an enhanced clinical course of EMC-D virus-induced diabetes, indicating that neither T cells nor B cells played a major role in the protection against EMC-D-virus-induced diabetes. Transfer of a large amount of antiserum to EMC-D-virus-infected mice protected the development of diabetes only when transferred within 36 h of infection, the timing of which was earlier than that for the production of natural neutralizing antibodied. Since pretreatment of mice with the macrophage-activating immunopotentiator Corynebacterium parvum (CP) completely prevented the development of diabetes, we studied the clinical outcome of EMC-D-virus-infected mice pretreated with CP. Mice treated with CP showed reduced proliferation of EMC-D virus in the affected organs, including the pancreas, while the levels of development of neutralizing antibody and serum interferon were not enhanced compared with the controls. Finally, we studied the macrophages derived from mice pretreated with CP and found that they inhibited the growth of EMC-D virus in vitro more than those derived from non-treated and thioglycolate-treated mice. Taken together, it can be suggested that neither T cells nor B cells, which have to do with adaptive immunity, play a significant role in the pathogenesis of EMC-D-virus-induced diabetes, while innate immunity, which is dependent on activated macrophages, contributes to in vivo resistance against EMC-D-virus-induced diabetes.

Patients with dilated cardiomyopathy possess insulin resistance independently of cardiac dysfunction or serum tumor necrosis factor-alpha.

It has recently been reported that insulin resistance is prevalent in patients with dilated cardiomyopathy (DCM); however, it remains unclear whether insulin resistance is directly induced by DCM or if it is caused by congestive heart failure associated with DCM. We evaluated homeostasis model assessment insulin resistance (HOMA-R) in 14 patients with DCM in comparison with 9 patients with valvular heart diseases (VHD). We also measured the level of serum tumor necrosis factor (TNF)-alpha as a possible causative factor for inducing insulin resistance. Even after the adjustment for age, body mass index, and cardiac function, HOMA-R was significantly higher in patients with DCM than in those with VHD (P = 0.012) (mean +/- SEM: 3.51 +/- 0.59, and 0.80 +/- 0.64, respectively). The serum TNF-alpha level tended to be higher in patients with DCM than in those with VHD; however, the difference was not significant. In conclusion, patients with DCM possess insulin resistance independently of the severity of cardiac dysfunction or serum TNF-alpha, suggesting that insulin resistance in patients with DCM may be closely associated with the pathogenic condition of DCM itself.