title: Dexamethasone treatment of lipopolysaccharide-induced meningitis in rabbits that mimics magnification of inflammation following antibiotic therapy.
abstract: The objective of adjunct anti-inflammatory therapy of bacterial meningitis is the containment of heightened inflammation caused by lysis of bacteria by antibiotics. This can be modelled by giving two consecutive intra-cisternal injections of lipopolysaccharide (LPS) to rabbits, the first at 0 h to induce inflammation to mimic that occurring during the proliferation of bacteria in the cerebrospinal fluid (CSF), and the second at 6 h to mimic inflammation subsequent to antibiotic-induced bacterial lysis. Injection of 2.5 ng of LPS induced pleocytosis at 4 h which was preceded by a peak of tumour necrosis factor (TNF) activity at 2 h. A subsequent injection of 25 ng of LPS at 6 h induced second peaks of pleocytosis and CSF TNF. Dexamethasone (1.5 mg/kg, i.v.) administered 15 min or 1 h before the second injection of LPS tended only to reduce CSF TNF, but effectively prohibited further pleocytosis. Brain TNF alpha mRNA levels were unchanged at 6 and 7 h after LPS injection, and were unaffected by dexamethasone. These results indicate that the subarachnoid space is distinct from the general circulation in that the TNF-producing cells present do not display a hypo-responsive state towards LPS as occurs when LPS is injected systemically. Furthermore, dexamethasone is able to attenuate the secondary inflammatory response resulting from a second LPS injection without eliminating a second peak of TNF activity.
authors.affiliation: Ceredigion Health Unit, Bronglais General Hospital, Aberystwyth, Dyfed, Wales.
authors.forename: P
authors.initials: P
authors.lastname: Rooney
authors.forename: G
authors.initials: G
authors.lastname: Bilbe
authors.forename: O
authors.initials: O
authors.lastname: Zak
authors.forename: T
authors.initials: T
authors.lastname: O'Reilly
mesh_terms: D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005947:Glucose / Q000032:analysis; D007773:Lactates / Q000032:analysis; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity*; D016920:Meningitis, Bacterial / Q000188:drug therapy*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013346:Subarachnoid Space / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
chemical_list: D002556:Cerebrospinal Fluid Proteins; D017931:DNA Primers; D007773:Lactates; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D005947:Glucose