title: Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites.
abstract: The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell production of interferon (IFN) gamma and inhibits T cell production of IL-4. We investigated the effects of IL-12 on cytokine gene expression, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil responses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma dependence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expression during primary and secondary N. brasiliensis infections and inhibited IL-3, IL-4, IL-5, and IL-9 gene expression during primary infections but had little inhibitory effect during secondary infections. IL-12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil responses during primary infections, but only eosinophil responses during secondary infections. IL-12 enhanced adult worm survival and egg production during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mucosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosal mastocytosis, and parasite survival and fecundity, but did not affect IL-12 inhibition of eosinophilia. These observations indicate that IL-12, if administered during the initiation of eosinophilia. These observations indicate that IL-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the production of Th-1 associated cytokines. However, IL-12 treatment has less of an effect once the production of Th2-associated cytokines has become established. In addition, our results provide evidence that Th2-associated responses protect against, and/or Th1-associated responses exacerbate, nematode infections.
authors.affiliation: Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
authors.forename: F D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: K B
authors.initials: KB
authors.lastname: Madden
authors.forename: A W
authors.initials: AW
authors.lastname: Cheever
authors.forename: I M
authors.initials: IM
authors.lastname: Katona
authors.forename: S C
authors.initials: SC
authors.lastname: Morris
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: B R
authors.initials: BR
authors.lastname: Hubbard
authors.forename: W C
authors.initials: WC
authors.lastname: Gause
authors.forename: J F
authors.initials: JF
authors.lastname: Urban
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12; D007378:Interleukins / Q000276:immunology*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D007422:Intestines / Q000469:parasitology; D007694:Killer Cells, Natural / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control
chemical_list: D016207:Cytokines; D007378:Interleukins; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma