Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis.

Abstract

Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 107 CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h.Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNFa antibodies given IC with 20 ng Hib LOS or 2 X 106 CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.

Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy

“…Thus, even with precocious therapeutic there is no longer sufficient time available for the action of dexamethasone in the sense of reducing the liberation of cytokines and their consequences, such as: the expression of adhesion glycoproteins between the polymorphonuclear and endothelial cells; the action of phospholipase A2 and nitric oxide synthase, among others 27,28 . This must be the same reason that explains the lesser effect of corticosteroid in the clinical trials (even in meningitis caused by S. pneumoniae and H. influenzae) 1,2,5 , in relation to studies and experiments with animal models, in which there is greater control of the onset of the infection and administration of dexamethasone [29][30][31][32] . …”

Differences of Pathophysiology in Experimental Meningitis Caused by Three Strains of Streptococcus Pneumoniae

“…Similar to endotoxin in the case of gramnegative organisms, cell-wall fragments can induce the release of interleukin-l, and to a lesser extent cachectin, from mononuclear cells [41]. In bacterial meningitis, these cytokines are essential in mediating the inflammatory changes and other pathophysiologic features of the disease, such as the disruption of the blood-brain barrier and the development of brain edema [42][43][44][45][46]. Future studies must examine whether the amount or pattern of cytokine release during meningitis affects the pathophysiologic spectrum of the disease and how characteristics of the infecting microorganism may be related to cytokine release.…”

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

“…Indeed, positive correlations have been observed between the degree of neuronal death during bacterial meningitis and the levels of TNF-a, IL-1b and IL-1R2. [12][13][14][15] Moreover, TNF-a concentrations are higher than normal in multiple sclerosis (MS) patients 16 and in Alzheimer's patients, 17 while TNF-a and IL-1b levels are increased in those afflicted by Parkinson's disease. 18 Moreover, TNF-a KO mice are protected against neuronal death in models of Parkinson's disease.…”