Cytokine profiles in heart, spleen, and thymus during the acute stage of experimental coxsackievirus B3-induced chronic myocarditis

Since cytokines play an important role in the pathogenesis of virus-induced chronic heart diseases, cytokine mRNA expression was studied in coxsackiev irus B3-infected NMRI mice during the acute phase of myocarditis until the onset of chronic cardiac disease. Virus replication, cytokine induction, in flammatory cell infiltration and myocardial damage were studied by titer de termination, reverse transcription-polymerase chain reaction (RT-PCR), and histopathology. To investigate whether the coxsackievirus B3-induced cytoki ne mRNA accumulation was only limited to the heart or generalized, spleen a nd thymus specimens were also included. Surprisingly, interleukin (IL)-10 a s a deactivator of T cell and macrophage functions was transcribed in the m yocardium nearly in parallel with virus replication from Day 1 through Day 14. At Day 3 p.i., the mRNA of IL-1 alpha, tumor necrosis factor (TNF)-alph a, IL-6, and interferon (IFN)-beta accumulated. At Days 4, 7, and 14, IL-12 -specific mRNA was produced. Furthermore, increasing amounts of IFN-gamma m RNA were found, whereas IL-2 and IL-4 mRNA remained undetectable. TNF-alpha , IL-1 alpha, IL-10, IL-12, and IFN-gamma mRNA persisted into the late stag e of myocarditis. In the spleen a closely correlated expression of virus an d IL-10-specific mRNAs was also found, and in addition, IFN-beta, TNF-alpha , and IL-6 were detected. In striking contrast to heart and spleen tissue, the distinct expression of viral RNA in the thymus was not accompanied by a n increased cytokine mRNA production. These data provide evidence for a uni que coxsackievirus B3-induced cytokine pattern in the myocardium and spleen and suggest that persistently expressed IL-10 may play a leading role in a cute and chronic myocarditis by subverting the immune response. J. Med. Vir ol. 61:578-526, 2000. (C) 2000 Wiley-Liss, Inc.