Glial cells production of inflammatory mediators induced by Streptococcus pneumoniae: inhibition by pentoxifylline, low-molecular-weight heparin and dexamethasone.
Exposure of primary rat glial cells to heat inactivated Streptococcus pneumoniae, induced dose-dependent production of tumor necrosis factor alpha (TNF alpha), nitric oxide (NO) and prostaglandin E2 (PGE2). Concomitant addition of the bacterium and the synthetic glucocorticoid dexamethasone resulted in complete suppression of TNF alpha, NO and PGE2 production. Pentoxifylline, a phosphodiesterase inhibitor completely blocked TNF alpha secretion, whereas NO and PGE2 were not affected. Low-molecular-weight heparin enoxaparin caused 25-64% inhibition in TNF alpha production, up to 30% inhibition of NO secretion and a 10% reduction in PGE2. Thus, Streptococcus pneumoniae, the pathogen most commonly associated with meningitis in the Western world can be added to the list of agents causing direct stimulation of glial cells. Pentoxifylline and enoxaparin in addition to dexamethasone may limit the central nervous system local inflammatory responses and could improve the effort towards reducing the dismal outcome of patients with pneumococcal meningitis.
Schwartz
D
D
Department of Pediatrics, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Engelhard
D
D
Gallily
R
R
Matoth
I
I
Brenner
T
T
D000818:Animals; D001921:Brain; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005333:Fetus; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D006495:Heparin, Low-Molecular-Weight; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003907:Dexamethasone; D015232:Dinoprostone; D010431:Pentoxifylline