Intrathecal treatment with the anti-phosphorylcholine monoclonal antibody TEPC-15 decreases neuronal damage in experimental pneumococcal meningitis

Chemotherapy. 2012;58(3):212-6. doi: 10.1159/000337287. Epub 2012 Jul 3.

Abstract

Background: Neuronal injury in pneumococcal meningitis is a consequence of microglial activation and direct toxicity by bacterial products and systemic inflammation.

Methods: The treatment effect of the TEPC-15 antibody recognizing teichoic and lipoteichoic acids was investigated in murine microglial cells and in a rabbit model of pneumococcal meningitis.

Results: In vitro, the TEPC-15 antibody recognizing teichoic and lipoteichoic acids increased Streptococcus pneumoniae phagocytosis by murine microglial cells. In rabbit ceftriaxone-treated S. pneumoniae meningitis, intracisternal TEPC-15 reduced the density of apoptotic neurons in the hippocampal dentate gyrus (116 ± 70 vs. 221 ± 132/mm(2); p = 0.03). Cerebrospinal fluid inflammatory parameters (protein, lactate, leukocytes, prostaglandins) were not reduced in TEPC-15-treated rabbits.

Conclusion: Intracisternal treatment with the TEPC-15 antibody reduced neuronal damage probably by promoting rapid phagocytosis of bacterial products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Ceftriaxone / therapeutic use
  • Cells, Cultured
  • Dentate Gyrus / drug effects
  • Disease Models, Animal
  • Lactic Acid / cerebrospinal fluid
  • Leukocytes / cytology
  • Leukocytes / immunology
  • Lipopolysaccharides / immunology
  • Meningitis, Pneumococcal / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Microglia / drug effects
  • Phagocytosis / drug effects
  • Prostaglandins / cerebrospinal fluid
  • Proteins / metabolism
  • Rabbits
  • Streptococcus pneumoniae / drug effects
  • Teichoic Acids / immunology

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Lipopolysaccharides
  • Prostaglandins
  • Proteins
  • Teichoic Acids
  • Lactic Acid
  • lipoteichoic acid
  • Ceftriaxone