Treatment with a monocolonal antibody to IL-8 attenuates the pleocytosis in experimental pneumococcal meningitis in rabbits when given intravenously, but not intracisternally.
The role of interleukin (IL)-8 as mediator in the recruitment of leucocytes into the CSF was investigated during experimental pneumococcal meningitis. Rabbits were inoculated intracisternally with approximately 10(6) CFU Streptococcus pneumoniae, and treated (i) intravenously with 5 mg of a monoclonal antibody to IL-8 (n = 7) or 5 mg of an isotype control antibody (n = 6); (ii) intracisternally with anti-IL-8, 100 microg (n = 5), 10 microg (n = 4), 1 microg (n = 4), 0.1 microg (n = 2). Ten rabbits served as untreated control group. Intravenous treatment with anti-IL-8 attenuated the pleocytosis significantly compared to untreated rabbits (P < 0.04) or rabbits treated with an isotype control antibody (P < 0.02). In contrast, intracisternal treatment with anti-IL-8 failed to attenuate the pleocytosis (P > 0.05). These results show, that IL-8 plays an important role in the recruitment of leucocytes during experimental pneumococcal meningitis, and that the functional activity of IL-8 in this process appears to be on the bloodstream side of the microvascular endothelium of the brain.
Ostergaard
C
C
Department of Research and Development, Statens Serum Institut, Copenhagen, Denmark. coa@ssi.dk
Yieng-Kow
R V
RV
Larsen
C G
CG
Mukaida
N
N
Matsushima
K
K
Benfield
T
T
Frimodt-Møller
N
N
Espersen
F
F
Kharazmi
A
A
Lundgren
J D
JD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001921:Brain / Q000098:blood supply / Q000276:immunology; D002946:Cisterna Magna; D004730:Endothelium, Vascular / Q000276:immunology; D007267:Injections; D007275:Injections, Intravenous; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D007964:Leukocytosis / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000150:complications / Q000276:immunology / Q000628:therapy*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D016209:Interleukin-8