Borrelia specific IFN-gamma and IL-4 secretion in CSF and blood during the course of Human Lyme Borreliosis: relation to clinical outcome

Widhe, Mona (1,2,4), Sara Jarefors (1,2,4), Christina Ekerfelt (1,4), Magnus Vrethem (3), Sven Bergström (5), Pia Forsberg (2,4), Jan Ernerudh (1,4)

1) Division of Clinical Immunology
2) Division of Infectious Diseases, Department of Molecular and Clinical Medicine; and
3) Division of Neurology and Neurophysiology, Department of Neuroscience and Locomotion
4) Clinical Research Centre, Faculty of Health Sciences, University of Linköping, and
5) Department of Microbiology, University of Umeå, Sweden

Borrelia specific IFN-gamma and IL-4 responses were analysed in 113 patients and controls with the sensitive ELISPOT method. Cerebrospinal fluid (CSF) and blood were collected during the disease course from patients with chronic or non-chronic neuroborreliosis and non-neuroborreliosis controls. Blood was drawn from patients with Lyme skin manifestations and healthy blood donors. Early increased Borrelia specific IFN-gamma secretion (p<0.05) and subsequent up-regulation of IL-4 (p<0.05) were detected in CSF cells of non-chronic neuroborreliosis.

In contrast, in CSF of chronic neuroborreliosis, persistent Borrelia specific IFN-gamma responses were observed (p<0.05). In erythema migrans, increased IFN-gamma (p<0.001) was observed early, whereas increased IL-4 (p<0.05) was observed after clearance. On the contrary, ACA patients showed Borrelia specific IFN-gamma (p<0.001), but not IL-4. Our data suggest that an initial IFN-gamma response followed by a subsequent up-regulation of IL-4 is associated with non-chronic manifestations, whereas a persistent IFN-gamma response may lead to chronic Lyme borreliosis.

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