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International Immunology 2005 17(10):1283-1291; doi:10.1093/intimm/dxh304
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Up-regulation of Borrelia-specific IL-4- and IFN-{gamma}-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis

Mona Widhe1,2,3,10, Barbro Hedin Skogman4,5, Sara Jarefors1,2,3, Mattias Eknefelt6, Gunilla Eneström7, Maria Nordwall8, Christina Ekerfelt1,3, Stefan Croner4,5, Sven Bergström9, Pia Forsberg2 and Jan Ernerudh1,3

1 Division of Clinical Immunology and 2 Division of Infectious Diseases, Department of Molecular and Clinical Medicine, 3 Clinical Research Center, Faculty of Health Sciences and 4 Division of Pediatrics, Department of Molecular and Clinical Medicine, University of Linköping, Sweden, 5 Pediatric Clinic, University Hospital, Linköping, Sweden, 6 Pediatric Clinic, Ryhov County Hospital, Jönköping, Sweden, 7 Pediatric Clinic, Västervik Hospital, Västervik, Sweden, 8 Pediatric Clinic, Vrinnevi Hospital, Norrköping, Sweden and 9 Department of Microbiology, University of Umeå, Sweden
10 Present address: Rheumatology Research Unit, Department of Medicine, CMM L8:04, Karolinska Institutet, SE-17176 Stockholm, Sweden

Correspondence to: M. Widhe; E-mail: mona.widhe{at}cmm.ki.se

The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-{gamma}, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN-{gamma}-secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN-{gamma} was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN-{gamma} responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

Keywords: cytokines, IL-4, IFN-{gamma}, immune response, ELISPOT

Transmitting editor: S. Romagnani


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