Transforming growth factor β2 inhibits cerebrovascular changes and brain edema formation in the tumor necrosis factor α-independent early phase of experimental pneumococcal meningitis

Abstract

Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor β (TGF-β) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-β on regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain edema formation during the early phase of experimental meningitis. Rats which were inoculated intracisternally with live pneumococci or with pneumococcal cell wall hydrolyzed by the M1 muramidase (PCW-M) developed an increase of rCBF and ICP within 4 h postintracisternal challenge. A single intraperitoneal injection of TGF-β2 but not of TGF-β2 vehicle-control prevented the changes of rCBF. Furthermore, TGF-β2 significantly reduced the increase of ICP in rats inoculated with PCW-M. Likewise, the devation of brain water content after intracisternal injection of pneumococci or PCW-M was blocked by pretreatment of rats with TGF-β2. TGF-β2 exhibited similar inhibitory effects in PCW-M-injected rats. The beneficial effects of TGF-β2 on the initial phase after pneumococcal inoculation seem to be tumor necrosis factor α-(TNF-α) independent since (a) intracistemal or intraperitoneal injection of neutralizing anti-TNF-α antibodies did not significantly influence rCBF, ICE and brain water content in PCW-M-induced meningitis; and (b) TNF-α was only occasionally detected at low levels in cerebrospinal fluid at 4 h after PCW-M application. © 1992, Rockefeller University Press., All rights reserved.