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

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.