Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro.
OBJECTIVE
alpha-Melanoycte stimulating hormone (alpha-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 alpha-MSH administration on Neisseria meningitidis infection of human meningeal cell cultures in vitro.


METHODS
Meningeal cell lines (n = 2) were infected with meningococci (10(2)-10(8) cfu/monolayer), isolated bacterial outer membranes (OM; 1 microg/ml) or lipo-oligosaccharide (LOS; 1 microg/ml) with and without alpha-MSH (10(-5)-10 microM). Bacterial adherence was quantified at 6 h, and cytokine production and microbicidal activity of alpha-MSH for meningococci were assessed at 24 h.


RESULTS
Compared with infection by meningococci alone, alpha-MSH (10 microM) up-regulated secretion of IL-6 and IL-8 (mean values increased from approximately 33 to 60 ng/ml), RANTES (mean values increased from approximately 26 to 105 ng/ml) and GM-CSF (mean values increased from approximately 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 alpha-MSH. Meningococci were resistant to the anti-microbial activity of alpha-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.
Kumar
Pawan
P
Division of Infection, Inflammation and Immunity, Department of Dermatopharmacology, University of Southampton Medical School, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Williams
Jeannette N
JN
Durkin
Kesta L
KL
Heckels
John E
JE
Friedmann
Peter S
PS
Healy
Eugene
E
Christodoulides
Myron
M
D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008578:Meninges / Q000187:drug effects / Q000382:microbiology* / Q000503:physiopathology*; D008585:Meningitis, Meningococcal / Q000378:metabolism / Q000503:physiopathology*; D009345:Neisseria meningitidis / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*
D015850:Interleukin-6; D016209:Interleukin-8; D000521:alpha-MSH; D000242:Cyclic AMP
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