The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis.

TLDR

Cytokines mediate many host responses to bacterial infections. The study aimed to determine the inflammatory activities of five cytokines—TNF‑α, IL‑1α, IL‑1β, MIP‑1, and MIP‑2—in the central nervous system. The authors assessed these activities in a rabbit model of meningeal inflammation. In this model, TNF‑α, IL‑1α, MIP‑1, and MIP‑2 increased blood‑brain barrier permeability, CSF leukocytosis, and brain edema, and neutralizing antibodies to these mediators, as well as anti‑CD‑18, abrogated these effects, while anti‑TNF or anti‑IL‑1 prevented inflammation and anti‑MIP‑1/2 only delayed onset, indicating that these cytokines drive inflammation and tissue damage in pneumococcal meningitis.

Abstract

Cytokines mediate many host responses to bacterial infections. We determined the inflammatory activities of five cytokines in the central nervous system: TNF-alpha, IL-1 alpha, IL-1 beta, macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2). Using a rabbit model of meningeal inflammation, each cytokine (except IL-1 beta) induced enhanced blood brain barrier permeability, leukocytosis in cerebrospinal fluid, and brain edema. Homologous antibodies to each mediator inhibited leukocytosis and brain edema, and moderately decreased blood brain barrier permeability. In rabbits treated with anti-CD-18 antibody to render neutrophils dysfunctional for adhesion, each cytokine studied lost the ability to cause leukocytosis and brain edema. After intracisternal challenge with pneumococci, antibodies to TNF or IL-1 prevented inflammation, while anti-MIP-1 or anti-MIP-2 caused only a 2-h delay in the onset of inflammation. We suggest these cytokines have multiple inflammatory activities in the central nervous system and contribute to tissue damage during pneumococcal meningitis.