Tumour necrosis factor alpha induces only minor inflammatory changes in the central nervous system, but augments experimental meningitis

• Published in: Neuroscience Vol. 86; no. 2; pp. 627 - 634
• Main Authors: Angstwurm, K, Freyer, D, Dirnagl, U, Hanisch, U.K, Schumann, R.R, Einhäupl, K.M, Weber, J.R
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Body Water - metabolism; Brain - blood supply; Brain - drug effects; Brain - physiopathology; Cell Wall; Cerebrovascular Circulation - drug effects; cytokine; Dose-Response Relationship, Drug; experimental; Guanidines - pharmacology; Inflammation - physiopathology; Intracranial Pressure - drug effects; Intracranial Pressure - physiology; Leukocyte Count; Male; Medical sciences; meningitis; Meningitis, Pneumococcal - physiopathology; Nervous system involvement in other diseases. Miscellaneous; Neurology; nitric oxide; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Regional Blood Flow - drug effects; Streptococcus pneumoniae; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - physiology; cytokine; c.f.u., colony forming units; nitric oxide; meningitis; ICP, intracranial pressure; rCBF, regional cerebral blood flow; TNF- α, tumour necrosis factor alpha; experimental; IL-1, interleukin-1; NOS, nitric oxide synthase; CSF, cerebrospinal fluid; PCW, pneumococcal cell wall; Nervous system diseases; Rat; Cytokine; Rodentia; Central nervous system; Inflammation; Vertebrata; Experimental disease; Mammalia; Animal; Nitric oxide; Central nervous system disease; Meningitis; Tumor necrosis factor α
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00032-3

Although tumour necrosis factor α is said to play a key role in bacterial meningitis and other CNS diseases, the effects of this proinflammatory cytokine have only been studied in part and incompletely understood. In a rat model, we investigated the effect of intracisternal injection of recombinant rat specific tumour necrosis factor α (5, 35, 70 and 280 μg tumour necrosis factor α) (i) alone, (ii) combined with pneumococcal cell wall components, on regional cerebral blood flow, intracranial pressure, white blood cell count in the cerebrospinal fluid, and brain water content. Tumour necrosis factor α dose-dependently caused an increase in regional cerebral blood flow (up to 221±43% of baseline values) over the six hours observation period and mild cerebrospinal fluid leukocytosis; intracranial pressure and brain water content were unchanged. Hypothesizing that regional cerebral blood flow changes are dependent on nitric oxide, tumour necrosis factor α induced regional cerebral blood flow increase was abolished by Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase. Combination of the lowest tumour necrosis factor α dose and a low dose pneumococcal cell wall preparation magnified the inflammatory effect of either. We conclude that intrathecally-injected tumour necrosis factor α alone results in only minor inflammatory changes, whereas it augments dramatically experimental meningitis.