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Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro

Pawan Kumar1, Jeannette N Williams, Kesta L Durkin

  • 1Division of Infection, Inflammation and Immunity, Department of Dermatopharmacology, University of Southampton Medical School, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|August 18, 2009
PubMed
Abstract

Insights

Alpha-melanocyte stimulating hormone (alpha-MSH) increased inflammation and bacterial adherence in meningococcal meningitis models. This neuropeptide is not suitable for treating meningitis due to these pro-inflammatory effects.

Area of Science:

  • Neuroimmunology
  • Microbiology

Background:

  • Alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide with known antimicrobial and immunomodulatory properties.
  • Alpha-MSH has been detected in cerebrospinal fluid of children with bacterial meningitis.

Purpose of the Study:

  • To investigate the therapeutic effects of alpha-MSH on Neisseria meningitidis infection in human meningeal cell cultures.
  • To assess the impact of alpha-MSH on bacterial adherence, cytokine production, and antimicrobial activity in vitro.

Main Methods:

  • Human meningeal cell lines were infected with Neisseria meningitidis, bacterial outer membranes, or lipo-oligosaccharide (LOS).
  • Cells were treated with varying concentrations of alpha-MSH.
  • Bacterial adherence, cytokine secretion (IL-6, IL-8, RANTES, GM-CSF), and antimicrobial activity were measured.

Main Results:

  • Alpha-MSH (10 microM) significantly upregulated secretion of IL-6, IL-8, RANTES, and GM-CSF.
  • Upregulated cytokine secretion correlated with a >5-fold increase in bacterial adherence, dependent on outer membrane components and LOS.
  • Neisseria meningitidis showed resistance to the antimicrobial activity of alpha-MSH at all tested concentrations.

Conclusions:

  • Alpha-MSH exhibits pro-inflammatory effects in vitro during meningococcal infection.
  • The synergistic action of alpha-MSH with bacterial components enhances adherence.
  • Alpha-MSH administration is contraindicated for the treatment of meningitis.

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