Protective Effect of a 21-Aminosteroid during Experimental Pneumococcal Meningitis

• Published in: The Journal of infectious diseases 1995-07, Vol.172 (1), p.113-118
• Main Authors: Lorenzi, Stefan, Koedel, Uwe, Frei, Karl, Bernatowicz, Andrea, Fontana, Adriano, Pfister, Hans-Walter
• Format: Article
• Language: English
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antioxidants - pharmacology; Astrocytes; Astrocytes - drug effects; Astrocytes - physiology; Biological and medical sciences; Blood flow; Body Water - metabolism; Brain - blood supply; Brain - drug effects; Brain - physiopathology; Cells, Cultured; Cerebrospinal Fluid - cytology; Cerebrovascular Circulation - drug effects; Cytokines; Disease Models, Animal; Infections; Interferon-gamma - pharmacology; Interleukin-6 - biosynthesis; Intracranial pressure; Intracranial Pressure - drug effects; Iron - pharmacology; Leukocyte Count - drug effects; Leukocytes - drug effects; Leukocytes - pathology; Lipid Peroxidation - drug effects; Lipids; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - physiology; Major Articles; Male; Medical sciences; Meningitis, Pneumococcal - physiopathology; Meningitis, Pneumococcal - prevention & control; Mice; Moisture content; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Pharmacology. Drug treatments; Pneumococcal meningitis; Pregnatrienes - pharmacology; Rats; Rats, Wistar; Reactive oxygen species; Recombinant Proteins; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/172.1.113

This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle and U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-a, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis.