Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro
Kumar, Pawan, Williams, Jeannette N., Durkin, Kesta L., Heckels, John E., Friedmann, Peter S., Healy, Eugene and Christodoulides, Myron (2010) Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro. Inflammation Research, 59, (2), 105-113. (doi:10.1007/s00011-009-0076-9).
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Description/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.
| Item Type: | Article |
|---|---|
| ISSNs: | 1023-3830 (print) |
| Related URLs: | |
| Keywords: | α-melanocyte stimulating hormone, neisseria meningitidis, meningitis, meningeal cell, cytokine and adherence |
| Subjects: | Q Science > QR Microbiology |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair |
| Item ID: | 72666 |
| Date Deposited: | 19 Feb 2010 |
| Last Modified: | 01 Jun 2011 09:58 |
| Contributors: | Kumar, Pawan (Author) Williams, Jeannette N. (Author) Durkin, Kesta L. (Author) Heckels, John E. (Author) Friedmann, Peter S. (Author) Healy, Eugene (Author) Christodoulides, Myron (Author) |
| Date: | February 2010 |
| Status: | Published |
| Contact Email Address: | mc4@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/72666 |
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