Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.
Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
X
X
Sáez-Llorens
H S
HS
Jafari
C
C
Severien
F
F
Parras
K D
KD
Olsen
E J
EJ
Hansen
I I
II
Singer
G H
GH
McCracken
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology*; D001929:Brain Edema / Q000276:immunology / Q000628:therapy*; D018821:CD18 Antigens; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008583:Meningitis, Haemophilus / Q000276:immunology / Q000628:therapy*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D003907:Dexamethasone