transforming-growth-factor-beta and Meningitis--Meningococcal

Meningitis is a serious disease mostly caused by viral or bacterial infections. In complicated cases it may lead to brain damage and death. The infection and cell damage result in a cellular and immunological response. Following this, a high secretion of cytokines can be expected. Cytokines, especially tumour necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), promote the inflammatory reactions in the subarachnoid space. Transforming growth factor beta 1 (TGF-beta 1) has antagonistic effects on TNF-alpha and IL-1-mediated processes. Therefore, it suppresses inflammatory reactions. To observe the expression of TGF-beta 1 in transcellular signalling in the inflammatory processes of meningitis, we investigated TGF-beta 1 mRNA in cells in the cerebrospinal fluid of three patients with meningitis by non-radioactive in situ hybridization. All patients fulfilled the usual clinical criteria of meningitis. In one case Neisseria menigitidis could be identified as the pathogenic agent. In the remainder, no agent could be isolated. In all cytological preparations of the cerebrospinal fluid of these patients a high level of TGF-beta 1 mRNA was detectable in the cell populations. It was possible to distinguish between the different cell types of the cerebrospinal fluid and to attach the mRNA expression to them. On the one hand, this makes it possible to investigate pathogenesis and defence mechanisms in bacterial and aseptic meningitis on a cellular level; on the other hand, it may open new perspectives in the control of disease development, prognosis, diagnosis and supporting therapy.

Topics: Adult; Cerebrospinal Fluid; Female; Humans; In Situ Hybridization; Male; Meningitis; Meningitis, Aseptic; Meningitis, Meningococcal; Microscopy, Fluorescence; RNA, Messenger; Signal Transduction; Transforming Growth Factor beta

Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor beta (TGF-beta) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-beta 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-beta 2 but not of TGF-beta 2 vehicle-control prevented the changes of rCBF. Furthermore, TGF-beta 2 significantly reduced the increase of ICP in rats inoculated with PCW-M. Likewise, the elevation of brain water content after intracisternal injection of pneumococci or PCW-M was blocked by pretreatment of rats with TGF-beta 2. TGF-beta 1 exhibited similar inhibitory effects in PCW-M-injected rats. The beneficial effects of TGF-beta 2 on the initial phase after pneumococcal inoculation seem to be tumor necrosis factor alpha- (TNF-alpha) independent since (a) intracisternal or intraperitoneal injection of neutralizing anti-TNF-alpha antibodies did not significantly influence rCBF, ICP, and brain water content in PCW-M-induced meningitis; and (b) TNF-alpha was only occasionally detected at low levels in cerebrospinal fluid at 4 h after PCW-M application.

Topics: Animals; Brain Edema; Cerebrovascular Circulation; Intracranial Pressure; Male; Meningitis, Meningococcal; Rats; Rats, Inbred Strains; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha