Coadministration of the cyanobacterial lipopolysaccharide antagonist CyP with antibiotic inhibits cytokine production by an in vitro meningitis model infected with Neisseria meningitidis.

Abstract

OBJECTIVES:

In this study, the objective was to determine the anti-inflammatory properties of CyP, a cyanobacterial lipopolysaccharide (LPS) antagonist, used in combination with antibiotic chemotherapy during infection of an in vitro meningitis model infected with Neisseria meningitidis (meningococcus).

METHODS:

Monocultures of human meningioma cells and meningioma-primary human macrophage co-cultures were infected with meningococci (10(2)-10(8) cfu/monolayer) or treated with isolated outer membranes or purified LPS (0.1-100 ng/monolayer) from N. meningitidis. CyP (1-20 μg/monolayer) was added at intervals from t = 0 to 4 h, with and without benzylpenicillin (1-20 μg/monolayer). The antagonistic effect of CyP and its adjunctive properties to benzylpenicillin administration was determined by measuring cytokine levels in culture supernatants after 24 h.

RESULTS:

CyP significantly inhibited (P < 0.05) the secretion of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and RANTES ('regulated upon activation, normal T cell expressed and secreted') (overall reduction levels from 50% to >95%) by meningioma cell lines and meningioma-macrophage co-cultures challenged with either live meningococci or bacterial components. Inhibition was effective when CyP was added within 2 h of challenge (P < 0.05) and was still pronounced by 4 h. In the co-culture model, CyP alone partially inhibited IL-1β secretion, but did not prevent tumour necrosis factor (TNF)-α secretion, whereas penicillin alone inhibited IL-1β and TNF-α but conversely did not reduce MCP-1 and RANTES secretion. However, coadministration of CyP and penicillin in both models had an additive effect and restored the overall inhibitory profile.

CONCLUSIONS:

CyP inhibits cytokine production in an in vitro meningitis model and augments the anti-inflammatory response when combined with benzylpenicillin. Administration of an LPS antagonist with antibiotic merits consideration in the emergency treatment of patients presenting with meningococcal infection.

• Authors: Rebecca Oliver, Karl J Staples, John Heckels, Carlo Rossetti, Monica Molteni, Myron Christodoulides
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 67 Issue 5 Pg. 1145-54 (May 2012) ISSN: 1460-2091 [Electronic] England
• PMID: 22334603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cytokines
• Immunologic Factors
• Lipopolysaccharides
• Penicillin G

Topics

• Anti-Bacterial Agents (pharmacology)
• Cells, Cultured
• Coculture Techniques
• Cytokines (metabolism)
• Epithelial Cells (immunology)
• Humans
• Immunologic Factors (pharmacology)
• Lipopolysaccharides (antagonists & inhibitors)
• Macrophages (immunology)
• Meningitis, Meningococcal (immunology, physiopathology)
• Neisseria meningitidis (immunology, pathogenicity)
• Penicillin G (pharmacology)