Systemically (but not intrathecally) administered IL-10 attenuates pathophysiologic alterations in experimental pneumococcal meningitis.
IL-10, a potent immunosuppressive cytokine, leads to macrophage/monocyte deactivation, inhibiting the production of cytokines and the release of reactive oxygen species and reactive nitrogen intermediates, which are known to be involved in the pathophysiology of bacterial meningitis. We investigated the effect of IL-10 on regional cerebral blood flow, intracranial pressure, cerebrospinal fluid (CSF) white blood cell count, and brain water content within 6 h after intracisternal (i.c.) pneumococcal challenge in a rat model of meningitis. Compared with IL-10 vehicle-injected infected rats, i.p. administration of 5 microg of IL-10 significantly attenuated the increase in regional cerebral blood flow, brain water content, intracranial pressure, and CSF white blood cell count, whereas a lower dosage of IL-10 (0.5 microg) was ineffective. The inhibitory effect of IL-10 (5 microg) was observed irrespective of time of IL-10 administration: just before, 1 h after, or 4 h after pneumococcal challenge. In contrast, i.c. application of IL-10 (5 microg) did not modulate these pathophysiologic parameters, and even augmented CSF pleocytosis. Moreover, i.c. injection of IL-10 alone induced meningeal inflammation in uninfected rats. IL-10 injected i.p., but not i.c., markedly inhibited the increase in IL-6 levels, as determined in CSF of infected animals. IL-10 suppressed the increase of nitrite concentration in cell culture supernatant of primary rat cerebral endothelial cells when stimulated with heat-killed pneumococci. The possible modes of action of IL-10 in pneumococcal meningitis may involve its interference with the production of nitric oxide or IL-6.
Koedel
U
U
Department of Neurology, Ludwig-Maximilians University of Munich, Klinikum Grosshadern, Germany.
Bernatowicz
A
A
Frei
K
K
Fontana
A
A
Pfister
H W
HW
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000166:cytology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D007427:Intracranial Pressure / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D008586:Meningitis, Pneumococcal / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D009569:Nitric Oxide