Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro
Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro
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.
?-melanocyte stimulating hormone, neisseria meningitidis, meningitis, meningeal cell, cytokine and adherence
105-113
Kumar, Pawan
63c79684-5e70-4733-926f-4bb516dfad1e
Williams, Jeannette N.
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Durkin, Kesta L.
a549115b-788e-4da6-898e-e5a532a6d788
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
February 2010
Kumar, Pawan
63c79684-5e70-4733-926f-4bb516dfad1e
Williams, Jeannette N.
14e675d9-8b05-4650-b01a-c52e73e903f4
Durkin, Kesta L.
a549115b-788e-4da6-898e-e5a532a6d788
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
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), .
(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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More information
Published date: February 2010
Keywords:
?-melanocyte stimulating hormone, neisseria meningitidis, meningitis, meningeal cell, cytokine and adherence
Identifiers
Local EPrints ID: 72666
URI: http://eprints.soton.ac.uk/id/eprint/72666
ISSN: 1023-3830
PURE UUID: 1cfb5e75-2493-4bf0-9db8-1a0acba12ef8
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Date deposited: 19 Feb 2010
Last modified: 14 Mar 2024 02:34
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Author:
Pawan Kumar
Author:
Jeannette N. Williams
Author:
Kesta L. Durkin
Author:
Peter S. Friedmann
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