IL-4 neutralization or TNF-alpha treatment ameliorate disease by an intracellular pathogen in IFN-gamma receptor-deficient mice.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

IL-4 neutralization or TNF-alpha treatment ameliorate disease by an intracellular pathogen in IFN-gamma receptor-deficient mice.

J Immunol. 1996 Dec 1;157(11):4746-50. Unique Identifier : AIDSLINE MED/97098698
Szalay G; Ladel CH; Blum C; Kaufmann SH; Department of Immunology, University of Ulm, Germany.

Abstract: Successful control of infectious disease depends on aquisition of an appropriate protective immune response. IFN-gamma, first produced by NK cells and then by Th1 cells, is central to acquired resistance against intracellular bacteria, including Listeria monocytogenes. In contrast, IL-4 is not generated to a measurable degree. Here we show that IL-4 is produced during listeriosis by IFN-gamma receptor gene disruption (IFN-gammaR(-/-)) mutant mice. Production of TNF was diminished, whereas IL-12 production was virtually unchanged in these mutants. Neutralization of IL-4 with anti-IL-4 mAb, as well as TNF-alpha reconstitution with rTNF-alpha, ameliorated listeriosis. These findings demonstrate the detrimental effects of IL-4 in listeriosis independent of IFN-gamma down-regulation and document the far-reaching consequences of a single cytokine deficiency on other cytokines. In cases where the primary gene defect cannot be restored, precise identification of secondary effects will promote rational immunotherapy based on neutralization or reconstitution of secondary immune deviations.

Keywords: Animal Antibodies, Monoclonal/PHARMACOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Immunotherapy In Vitro Interferon Type II/BIOSYNTHESIS/*DEFICIENCY/GENETICS Interleukin-4/*ANTAGONISTS & INHIB/BIOSYNTHESIS Listeria Infections/*IMMUNOLOGY/PREVENTION & CONTROL/*THERAPY Mice Mice, Inbred C57BL Mice, Knockout Neutralization Tests Spleen/IMMUNOLOGY Support, Non-U.S. Gov't Th2 Cells/IMMUNOLOGY Time Factors Tumor Necrosis Factor/BIOSYNTHESIS/*PHARMACOLOGY JOURNAL ARTICLE
970228
M9721856

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