Borrelia-Specific interferon-γ 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-γ (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-γ (P < .001), but not IL-4, detected in blood samples. The present data suggest that an initial IFN-gamma response, followed by upregulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN-gamma response may lead to chronic Lyme borreliosis.