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

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Abstract

Objective and design

α-Melanoycte stimulating hormone (α-MSH), a neuropeptide hormone with reported anti-microbial and immuno-modulatory properties in vitro, has previously been detected in the cerebrospinal fluid of children with bacterial meningitis. We investigated the therapeutic effects of α-MSH administration on Neisseria meningitidis infection of human meningeal cell cultures in vitro.

Materials and methods

Meningeal cell lines (n = 2) were infected with meningococci (102–108 cfu/monolayer), isolated bacterial outer membranes (OM; 1 μg/ml) or lipo-oligosaccharide (LOS; 1 μg/ml) with and without α-MSH (10−5–10 μM). Bacterial adherence was quantified at 6 h, and cytokine production and microbicidal activity of α-MSH for meningococci were assessed at 24 h.

Results

Compared with infection by meningococci alone, α-MSH (10 μM) up-regulated secretion of IL-6 and IL-8 (mean values increased from ~33 to 60 ng/ml), RANTES (mean values increased from ~26 to 105 ng/ml) and GM-CSF (mean values increased from ~0.3 to 1 ng/ml; P < 0.05). Upregulated secretion correlated with a neuropeptide-mediated rapid and >5-fold increase (P < 0.05) in bacterial adherence to cells and was dependent on OM components including LOS acting synergistically with α-MSH. Meningococci were resistant to the anti-microbial activity of α-MSH at all concentrations tested.

Conclusions

Our study demonstrates that a potentially therapeutic neuropeptide exerts pro-inflammatory effects during meningococcal infection in vitro and its use in the treatment of meningitis is contra-indicated.

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Acknowledgments

P.K. was a PhD student supported by the British Skin Foundation. The work was supported by funding from the British Skin Foundation and the Meningitis Research Foundation.

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Authors and Affiliations

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

    Pawan Kumar, Peter S. Friedmann & Eugene Healy

  2. Neisseria Research Group, Molecular Microbiology, Division of Infection, Inflammation and Immunity, University of Southampton Medical School, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Jeannette N. Williams, Kesta L. Durkin, John E. Heckels & Myron Christodoulides

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  1. Pawan Kumar
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  2. Jeannette N. Williams
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  3. Kesta L. Durkin
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  4. John E. Heckels
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  6. Eugene Healy
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Correspondence to Myron Christodoulides.

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Responsible Editor: G. Wallace.

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Kumar, P., Williams, J.N., Durkin, K.L. et al. Neuropeptide α-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro. Inflamm. Res. 59, 105–113 (2010). https://doi.org/10.1007/s00011-009-0076-9

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  • DOI: https://doi.org/10.1007/s00011-009-0076-9

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