ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 15 P306

The novel role of vitamin D in the fight against gram negative bacterial meningitis

Luke Materacki, Alex Sinclair, Pamela Khosla, Claire Onyimba, S John Curnow, Elizabeth Walker & Saaeha Rauz

University of Birmingham, Birmingham, UK.

Gram negative bacterial meningitis with consequent meningeal inflammation is a major cause of death and morbidity worldwide. Meningitis denotes infection of the blood brain barrier (BBB) including the choroid plexus (CP), the site of secretion of cerebrospinal fluid (CSF). We propose that 1α 25-dihydroxyvitamin D3 (1α25-(OH)2D3), an important immunomodulator, may suppress CP inflammation thereby reducing morbidity. We aimed to assess the effects of 1α25-(OH)2D3 in a primary human choroid plexus epithelial (HCPEpi) cell line in the context of gram negative bacterial infection, simulated by using lipopolysacharide (LPS) endotoxin.

HCPEpi cells were incubated with 1 μgml−1 LPS in the presence and absence of 1 μM 1α25-(OH)2D3 for 4, 8 and 12 h. Expression of key elements of the vitamin D pathway (toll like receptor 4 (TLR4), vitamin D receptor (VDR), 25-hydroxyvitamin D3−1α hydroxylase (1αOH), 25-hydroxyvitamin D3-24 hydroxylase (24OH), interleukin (IL)-6, IL-8 and IL-1β) were confirmed using reverse transcription polymerase chain reaction (PCR). Treatment with LPS and 1α25-(OH)2D3 demonstrated induction of IL-6, IL-8 and IL-1β mRNA using real-time PCR. Analysis of these cell culture supernatants using multiplex bead immunoassays illustrated up-regulation of IL-6, tumour necrosis factor α (TNFα) and interferon γ (IFNγ) protein.

We have identified that 1α25-(OH)2D3 induces early pro-inflammatory actions in HCPEpi cells immediately following LPS recognition. The late actions of 1α25-(OH)2D3 in meningitis remain to be explored. The early inflammatory reaction may represent an important step in mounting an immune response against gram negative pathogens. Manipulation of local production of vitamin D may therefore have a role in the treatment of gram negative bacterial meningitis.

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