engleski

Serum and cerebrospinal fluid antiviral cytokine profile in tick-borne encephalitis

Background: Tick-borne encephalitis (TBE) is the most important re-(emerging) arboviral zoonosis in Europe. Although up to 80% of TBE cases are asymptomatic or presented as mild febrile illness, 20-40% patients develop neuroinvasive disease (meningitis, meningoencephalitis, meningoencephalomyelitis). While clinical characteristics of TBE are well described, data on the antiviral cytokine response to TBEV are limited. Methods: A total of 32 serum and 16 cerebrospinal fluid (CSF) samples from 33 patients with TBE were included in the study. A multiplex bead-based assay for the simultaneous quantification of 13 human antiviral cytokines was used. The panel included cytokines associated with innate and early pro-inflammatory immune responses: TNF-α, IL-6, IL-2, IFN-γ ; Th2 immune response: IL-4, IL-5, IL-9, IL-13 ; Th17 immune response: IL-17A, IL-17F, IL-21, IL-22 and the key anti-inflammatory cytokine IL-10. Results: Neuroinvasive infection was documented in 29/87.8% patients (meningitis 18/54.5%, meningoencephalitis 11/33.3%), while 4/12.2% of patients presented with nonspecific febrile disease. Significantly higher concentrations of IL-6 in the CSF vs. serum were found in paired CSF/serum samples (median 780.88 pg/mL, IQR 130.81-3, 077.66 vs. median 23.25 pg/mL, IQR 7.79-27.09 ; p<0.001). There was no significant difference in the CSF IL-6 concentration in patients with meningitis (median 2648.1 pg/mL, IQR 276.75-3077.66) and meningoencephalitis (median 143.46 pg/mL, IQR 102.88- 1219.94 ; p=0.28). IFN-γ levels were higher in CSF compared to serum, however these differences were not significant (median 122.71 pg/mL, IQR 98.09-246.04 vs. 27.28 pg/mL, IQR 14.81-37.75 ; p=0.12). IL-22 and IL-5 were detectable in both serum and cerebrospinal fluid (CSF) of TBE patients [(IL-22 serum median 10.84 pg/ml, IQR 7.90-14.05 ; CSF median 5.82 pg/ml, IQR 3.72-15.72), (IL-5 serum median 11.35 pg/mL, IQR 3.85-19.64, CSF median 15.04 pg/mL, IQR 4.02- 46.82)], while expression of IL-2, IL-4, TNF-α and Th1 17 cytokines (IL-17A, IL-17F, IL-21) was detected only in the serum samples. Conclusions: Increased levels of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the central nervus system of patients with TBE. Expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.

serum ; cerebrospinal fluid ; cytokine ; tick-borne encephalitis

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