Inhibition of complement-factor-5a-induced inflammatory reactions by prostaglandin E2 in experimental meningitis.
The possible role of complement factor 5a (C5a) and prostaglandin E2 (PGE2) in cerebrospinal fluid (CSF) pleocytosis and protein accumulation was assessed in a rabbit model of meningitis. Intracisternally administered C5a caused a rapid, early influx of leukocytes into CSF that peaked at 1 h after injection; by 6 h, cell counts were slightly higher than those in controls. Administration of PGE2 or saline did not induce detectable CSF leukocytosis. Coadministration of PGE2 with C5a decreased CSF leukocytosis in a dose-related fashion. Protein concentration increased 30 min after administration of C5a, peaked after 1 h, and remained elevated for 6 h. PGE2 caused a dose-related increase in protein content after 2 h, whereas coadministration caused an inversely dose-related inhibition of the C5a-induced protein influx into CSF. These data suggest that PGE2 in the subarachnoid space exerts an inhibitory action on the C5a-mediated response that is probably not related to its direct effects on protein extravasation.
Kadurugamuwa
J L
JL
Pharmaceutical Research Laboratories, CIBA-GEIGY Ltd., Basel, Switzerland.
Hengstler
B
B
Bray
M A
MA
Zak
O
O
D000818:Animals; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D015936:Complement C5a / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000276:immunology; D015232:Dinoprostone / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000276:immunology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007958:Leukocyte Count; D007964:Leukocytosis / Q000134:cerebrospinal fluid; D008297:Male; D008586:Meningitis, Pneumococcal / Q000276:immunology*; D011817:Rabbits
D002556:Cerebrospinal Fluid Proteins; D015936:Complement C5a; D015232:Dinoprostone