Document 0345
 DOCN  M9590345
 TI    Studies of cytokine activity in virus infection in vivo using
       recombinant viruses and cytokine gene knockout mice.
 DT    9509
 AU    Ramsay AJ; Ramshaw IA; Viral Engineering and Cytokine Research Group,
       John Curtin School; of Medical Research, Australian National University,
       Canberra.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:152 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291754
 AB    Cytokines play a determinant role in antiviral immune responses both in
       the inductive and effector phases. We have used mice rendered deficient
       for the production of particular cytokines (GKO mice) and recombinant
       vaccinia viruses (rVV) encoding these factors in order to study some of
       the activities of cytokines in a model of virus infection. Using this
       approach, we have shown, in collaboration with Alan Husband, that
       interleukin (IL)-6 is crucial for the development of mucosal antibody
       responses in vivo. IL-6 GKO mice control VV infection as well as
       controls but mount grossly deficient mucosal IgA and IgG responses.
       These findings confirm that IL-6 is important for the normal development
       of specific mucosal IgA and IgG responses in vivo, but not for the
       development of CMI, at least against rVV. The crucial role of this
       factor for IgA and IgG production was confirmed by the ability of
       vector-expressed IL-6 to completely restore the deficient response.
       Cytokines are also important determinants of CMI responses and we have
       shown that IL-4 markedly downregulates antiviral CMI in vivo and
       exacerbates infection, a feature which may underlie the development of
       chronicity or disease progression (e.g. in HIV infection). In contrast,
       interferons, IL-12 and TNF mediate antiviral CMI in our system and may
       be used to selectively stimulate such responses. We are currently
       studying their interactions in this regard, using rVV encoding these
       factors in mice with the relevant genes disrupted.
 DE    Animal  Cytokines/GENETICS/*PHYSIOLOGY  IgA,
       Secretory/GENETICS/PHYSIOLOGY  IgG/GENETICS/PHYSIOLOGY
       Interleukin-6/GENETICS/PHYSIOLOGY  Mice  Mice, Knockout  *Recombination,
       Genetic  Vaccinia Virus/GENETICS/*IMMUNOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).