ROLE OF MACROPHAGE CYTOKINES IN INFLUENZA-A VIRUS-INFECTIONS

Human monocytes and murine macrophages were found to be susceptible to infection by influenza A virus. Although virus replication was low, i nfection led to cell death which was characterized by an extreme intra cellular vacuolization. Most importantly, influenza A virus infection was accompanied by a particular pattern of cytokine release. Whereas I L-1 beta, IL-6 and TNF-alpha production was dependent on exposure to i nfectious virus, IFN-alpha/beta release was also induced by UV-inactiv ated virus. Although influenza A virus infection alone induced a subst antial cytokine mRNA accumulation, translation into bioactive cytokine protein was rather limited. However, addition of low LPS concentratio ns was capable of strongly potentiating cytokine release from virus-in fected cells. Thus, in a first step, an influenza A virus infection pr imes mononuclear phagocytes by leading to an accumulation of cytokine mRNA which, in a second step, may be readily translated into bioactive cytokines when triggering signals such as LPS are available. These fi ndings suggest that influenza A virus represents an ultimately fatal m acrophage activating factor which, when inducing moderate amounts of c ytokines, may be beneficial by mounting an immediate antiviral respons e, but which may cause adverse effects when cytokine release is highly elevated by bacterial products.