title: IL-1 and TNF-alpha play a pivotal role in the host immune response in a mouse model of Staphylococcus aureus-induced experimental brain abscess.
abstract: Brain abscesses represent a significant medical problem despite recent advances made in detection and therapy. Using an established Staphylococcus aureus-induced brain abscess model, we have sought to define the functional importance of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6 in the host anti-bacterial immune response using cytokine gene knockout (KO) mice. Previous studies from our laboratory revealed that these cytokines are among the main proinflammatory mediators produced during the acute stage of brain abscess development. The results presented here demonstrate that although they share many redundant activities, IL-1 and TNF-alpha are important for containing bacterial infection in evolving brain abscesses as evident by increased mortality and bacterial burdens in IL-1 and TNF-alpha KO mice compared to wild type (WT) animals. In contrast, IL-6 was not found to be a major contributor to the host anti-bacterial immune response. Microarray analysis was used to evaluate the downstream consequences originating from the lack of IL-1 on subsequent proinflammatory mediator expression in brain abscesses from IL-1 KO and WT animals. Although numerous genes were significantly induced following S. aureus infection, only IL-1beta and 2 chemokines, CCL9 (macrophage inflammatory protein-1 gamma/MIP-1gamma) and CXCL13 (B lymphocyte chemoattractant/BLC), were differentially regulated in IL-1 KO versus WT animals. These results suggest that IL-1 and TNF-alpha play a pivotal role during the acute stage of brain abscess development through regulating the ensuing anti-bacterial inflammatory response.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. KielianTammyL@uams.edu
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
authors.forename: Edward D
authors.initials: ED
authors.lastname: Bearden
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Baldwin
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen
mesh_terms: D000818:Animals; D001922:Brain Abscess / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha