Up-regulation of Borrelia-specific IL-4- and IFN-
-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis
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-
, 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--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- 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- 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-, immune response, ELISPOT