Chemokines CXCL10 and CXCL11 in the cerebrospinal fluid of patients with tick-borne encephalitis.

OBJECTIVES: The aim of our study was to determine whether cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE) contains CXCL10, CXCL11, p40 subunit of interleukin-12 (IL-12)/IL-23, IL-18 and IL-15. We compared serum and CSF concentrations of CXCL10 and analysed the possible concentration gradient of this chemokine between the periphery and central nervous system. MATERIALS AND METHODS: The study enrolled 19 TBE patients and 10 patients with non-inflammatory neurological diseases. RESULTS: CSF of TBE patients contained CXCL10 (median 217 pg/ml), CXCL11 (8.3 pg/ml), p40 subunit of IL-12/IL-23 (38.9 pg/ml), IL-18 (30.1 pg/ml) and IL-15 (5.9 pg/ml). CXCL10 in the CSF of TBE patients was higher compared with serum (median 62 pg/ml, P < 0.001). CONCLUSION: CSF of TBE patients contains CXCL10, CXCL11, p40 subunit of IL-12/IL-23, IL-18 and IL-15. Increased CXCL10 concentration in CSF suggests a role for this chemokine in the recruitment of CXCR3-expressing T-cells into the CSF of TBE patients.

Synthesis of novel adamantylacetyl derivative of peptidoglycan monomer--biological evaluation of immunomodulatory peptidoglycan monomer and respective derivatives with lipophilic substituents on amino group.

Novel synthetic analogue of immunomodulatory peptidoglycan monomer 1 (PGM), (adamant-1-yl)-CH2CO-PGM (2), was prepared by acylation of epsilon-amino group of diaminopimelic acid with symmetrical (adamant-1-yl)-acetic acid anhydride in the presence of triethylamine. The product was isolated by gel filtration on Sephadex G-25, followed by ion exchange chromatography on SP-Sephadex C-25. The susceptibility of (adamant-1-yl)-CH2CO-PGM to hydrolysis with N-acetylmuramyl-L-alanine amidase was demonstrated, and the product of hydrolysis, (adamant-1-yl) CH2CO-pentapeptide 3, was characterized. Both 2 and 3 are water soluble and non-pyrogenic compounds. Immunomodulatory activity of PGM (adamant-1-yl)-CH2CO-PGM and structurally related derivative Boc-Tyr-PGM was compared in experiments in vivo, in mice, using ovalbumin (OVA) as an antigen. All three tested compounds exhibited comparable immunostimulating effects with respect to the induction of anti-ovalbumin immunoglobulin G. The results of evaluation of biological activity show that the substitution of free amino group in the parent peptidoglycan molecule with bulky lipophilic substituents did not affect the susceptibility to hydrolysis with N-acetylmuramyl-L-alanine amidase and did not alter markedly the immunostimulating activity. The results also indicate that the free amino group in the peptide chain is not a necessary requirement in the mechanism of immunostimulation of tested immunomodulators.