Borrelia-specific interferon-gamma and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome.
The Borrelia-specific interferon (IFN)- gamma and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN- gamma (P<.05) and subsequent up-regulation of IL-4 (P<.05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN- gamma responses were observed in the CSF cells of patients with chronic NB (P<.05). In patients with erythema migrans, increased IFN- gamma (P<.001) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 (P<.05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN- gamma (P<.001), but not IL-4, detected in blood samples. The present data suggest that an initial IFN- gamma response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN- gamma response may lead to chronic Lyme borreliosis.
Widhe
Mona
M
Divisions of Clinical Immunology and Infectious Diseases, Department of Molecular and Clinical Medicine, Linkoping University, Linkoping, Sweden. mona.widhe@imk.liu.se
Jarefors
Sara
S
Ekerfelt
Christina
C
Vrethem
Magnus
M
Bergstrom
Sven
S
Forsberg
Pia
P
Ernerudh
Jan
J
D000169:Acrodermatitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D025065:Borrelia burgdorferi / Q000276:immunology*; D015787:Erythema Chronicum Migrans / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007371:Interferon-gamma / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D020852:Lyme Neuroborreliosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000276:immunology*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015847:Interleukin-4; D007371:Interferon-gamma