Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat

Sik Kim Kwang Sik Kim, C. A. Wass, A. S. Cross, S. M. Opal

Research output: Contribution to journalArticlepeer-review

Abstract

In an attempt to understand the role of TNF in the central nervous system (CNS) pathophysiologic events associated with bacterial meningitis, we examined the effect of intravenous vs. intracisternal administration of TNF alpha on penetration of circulating 125I-labeled albumin into cerebrospinal fluid (CSF) and CSF white blood cell (WBC) counts in rats. Intracisternal administration of tumor necrosis factor alpha (TNF-α) resulted in dose- and time-dependent alterations of the CSF penetration and CSF WBCs, while intravenous administration of TNF-α did not induce any changes. These changes by intracisternal TNF were abolished by heat treatment of TNF or coadministration of MAb to TNF-α. Mab to TNF-α also significantly reduced the CSF penetration of circulating albumin in experimental hematogenous Haemophilus influenzae type b meningitis in infant rats but this salutary effect required both intravenous and intracisternal administration. However, MAb to TNF-α failed to affect CSF pleocytosis in experimental hematogenous meningitis. These findings suggest that some of CNS pathophysiologic changes in bacterial meningitis may be a result of the local production of TNF but other host inflammatory responses may also participate in CNS inflammation in hematogenous bacterial meningitis.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalLymphokine and Cytokine Research
Volume11
Issue number6
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Hematology

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