title: Effect of recombinant human macrophage colony-stimulating factor 1 on immunopathology of experimental brucellosis in mice.
abstract: Brucella abortus injected into CBA mice replicated primarily in the spleen and liver, reaching a peak bacterial count in both organs about 7 days postinfection. The organism was eliminated from the liver but declined to a chronic phase in the spleen. The infection caused hepatosplenomegaly. An influx of macrophages into the two organs was monitored by quantitative Northern (RNA blot) analysis of the macrophage-specific marker lysozyme mRNA. Lysozyme mRNA was detectable in spleen and increased three- to fourfold during infection. In liver, lysozyme mRNA was initially undetectable, but at about the peak of infection it reached a level comparable to that in the spleen. Macrophage colony-stimulating factor 1 (CSF-1) has been reported to be elevated in the circulation of animals infected with B. abortus and is known to stimulate monocytopoiesis. To investigate the role of CSF-1 in pathogenesis, we studied the effect of further increasing the CSF-1 concentration by administration of recombinant human CSF-1. Since the infection is characterized by several distinct phases, recombinant human CSF-1 was administered at defined times relative to these phases. Pronounced effects were observed only when CSF-1 administration was begun during the developing acute phase. The consequences were decreased bacterial numbers in the spleen but an increase in the liver, reduced antibody generation, and increased hepatosplenomegaly. A feature of many chronic intracellular infections is immunosuppression. B. abortus caused a substantial diminution of responsiveness of spleen cells to T-cell mitogens, particularly concanavalin A. This action was mimicked by CSF-1 treatment of the animals prior to spleen cell isolation. The results suggest that CSF-1 plays a role in macrophage recruitment in brucellosis and that recruited macrophages contribute to the immunopathology and immunosuppression.
authors.affiliation: Department of Microbiology, University of Queensland, St. Lucia, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Doyle
authors.forename: W J
authors.initials: WJ
authors.lastname: Halliday
authors.forename: C J
authors.initials: CJ
authors.lastname: Barnett
authors.forename: T L
authors.initials: TL
authors.lastname: Dunn
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015152:Blotting, Northern; D002006:Brucellosis / Q000188:drug therapy* / Q000276:immunology; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D006529:Hepatomegaly / Q000209:etiology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology / Q000382:microbiology; D008168:Lung / Q000033:anatomy & histology; D008213:Lymphocyte Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009113:Muramidase / Q000096:biosynthesis; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000033:anatomy & histology / Q000201:enzymology / Q000382:microbiology; D013163:Splenomegaly / Q000209:etiology; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D009113:Muramidase