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).

Abstract

Objective and design: ?-Melanoycte stimulating hormone (?-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 ?-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 ?g/ml) or lipo-oligosaccharide (LOS; 1 ?g/ml) with and without ?-MSH (10?5–10 ?M). Bacterial adherence was quantified at 6 h, and cytokine production and microbicidal activity of ?-MSH for meningococci were assessed at 24 h.

Results: compared with infection by meningococci alone, ?-MSH (10 ?M) 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 ?-MSH. Meningococci were resistant to the anti-microbial activity of ?-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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Contributors

Author: Myron Christodoulides

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