Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infection

Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is acc ompanied by an intense mononuclear leukocyte infiltration. Because myocardi al tissue damage may either result from viral infections or from a dysregul ated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived ma crophages yielded a low amount of new viruses, which led to cell death. Alt hough CVB3 infection induced the mRNA for the proinflammatory cytokines tum or necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, only li ttle cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persis tently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macroph ages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy. J. Med. Virol. 64:487-498, 2001. (C) 2001 Wiley-Liss, Inc.