title: Role of macrophage cytokines in influenza A virus infections.
abstract: Human monocytes and murine macrophages were found to be susceptible to infection by influenza A virus. Although virus replication was low, infection led to cell death which was characterized by an extreme intracellular vacuolization. Most importantly, influenza A virus infection was accompanied by a particular pattern of cytokine release. Whereas IL-1 beta, IL-6 and TNF-alpha production was dependent on exposure to infectious virus, IFN-alpha/beta release was also induced by UV-inactivated virus. Although influenza A virus infection alone induced a substantial cytokine mRNA accumulation, translation into bioactive cytokine protein was rather limited. However, addition of low LPS concentrations was capable of strongly potentiating cytokine release from virus-infected cells. Thus, in a first step, an influenza A virus infection primes 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 findings suggest that influenza A virus represents an ultimately fatal macrophage activating factor which, when inducing moderate amounts of cytokines, may be beneficial by mounting an immediate antiviral response, but which may cause adverse effects when cytokine release is highly elevated by bacterial products.
authors.affiliation: Institute of Immunology, Philipps University, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Peschke
authors.forename: A
authors.initials: A
authors.lastname: Bender
authors.forename: M
authors.initials: M
authors.lastname: Nain
authors.forename: D
authors.initials: D
authors.lastname: Gemsa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides