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*
Department of Virology, National Public Health Institute, Helsinki, Finland; and
Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan
Monocytes and macrophages play a significant role in host’s
defense system, since they produce a number of cytokines in response to
microbial infections. We have studied IL-1ß, IL-18, IFN-
/ß, and
TNF- gene expression and protein production in human primary
monocytes and GM-CSF-differentiated macrophages during influenza A and
Sendai virus infections. Virus-infected monocytes released only small
amounts of IL-1ß or IL-18 protein, whereas 7- and 14-day-old
GM-CSF-differentiated macrophages readily produced these cytokines.
Constitutive expression of proIL-18 was seen in monocytes and
macrophages, and the expression of it was enhanced during
monocyte/macrophage differentiation. Expression of IL-18 mRNA was
clearly induced only by Sendai virus, whereas both influenza A and
Sendai viruses induced IL-1ß mRNA expression. Since caspase-1 is
known to cleave proIL-1ß and proIL-18 into their mature, active
forms, we analyzed the effect of a specific caspase-1 inhibitor on
virus-induced IL-1ß and IL-18 production. The release of IL-1ß and
IL-18, but not that of IFN-/ß or TNF-, was clearly blocked by
the inhibitor. Our results suggest that the cellular differentiation is
a crucial factor that affects the capacity of monocytes/macrophages to
produce IL-1ß and IL-18 in response to virus infections. Furthermore,
the virus-induced activation of caspase-1 is required for the efficient
production of biologically active IL-1ß and
IL-18.
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