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Objective: There have been few reports on the role of Intercellular Adhesion Molecule 1 (ICAM-1), but not interleukin-21 (IL-21) and interleukin-23 (IL-23) in tick-borne encephalitis (TBE) and neuroborreliosis (NB). We postulate that these two interleukins may participate in the early phase of TBE and NB. The aim of the study was to measure serum and cerebrospinal fluid (CSF) concentration of ICAM-1, IL-21 and IL-23 in patients with TBE and NB before treatment and to assess their usefulness in the diagnosis and monitoring of inflammatory process in TBE and NB., Methods: Forty-three patients hospitalized in The Department of Infectious Diseases and Neuroinfections of Medical University in Bialystok, Poland, were included in the study. Patients were divided into three groups: TBE, NB and CG. Pre-treatment blood and CSF samples were obtained from all patients. ELISA kits (DRG Instruments, Germany) were used to measure the concentration of IL-21, IL-23 and sICAM-1., Results: Significant differences between TBE/CG and NB/CG concentration of sICAM-1 were found only in the CSF. CSF IL-21 levels in NB were lower than in TBE. In TBE, a strong negative correlation between CSF concentration of IL-21 and IL-23 and monocyte count in CSF was observed. Negative correlation between IL-21 in CSF and neutrophil count was also noted. Serum IL-23 correlated positively with leukocytes and platelet count in serum. In NB, a strong positive correlation between serum IL-21 and platelet count and negative correlation between IL-21 in serum and CSF with pleocytosis was observed., Conclusions: Increased sICAM-1 concentration in TBE and NB may be a proof of brain-blood barrier disturbances in the early phase of these diseases. IL-21 and IL-23 do not appear to play an important role in the pathogenesis of the early stages of TBE and NB., (Copyright © 2012 Elsevier Ltd. All rights reserved.)