IL-1 and TNF-α Play A Pivotal Role in the Host Immune Response in A Mouse Model of Staphylococcus aureus-Induced Experimental Brain Abscess

Tammy Kielian, Edward D. Bearden, Aaron C. Baldwin, Nilufer Esen

Research output: Contribution to journalArticle

88 Scopus citations

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-α), 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-α are important for containing bacterial infection in evolving brain abscesses as evident by increased mortality and bacterial burdens in IL-1 and TNF-α 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-1β and 2 chemokines, CCL9 (macrophage inflammatory protein-1 gamma/MIP-1γ) and CXCL13 (B lymphocyte chemoattractant/BLC), were differentially regulated in IL-1 KO versus WT animals. These results suggest that IL-1 and TNF-α play a pivotal role during the acute stage of brain abscess development through regulating the ensuing anti-bacterial inflammatory response.

Original languageEnglish (US)
Pages (from-to)381-396
Number of pages16
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number4
DOIs
StatePublished - Apr 2004

    Fingerprint

Keywords

  • Brain abscess
  • Interleukin-1 (IL-1)
  • S. aureus
  • Tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this