INTERLEUKIN-6 IS EXPRESSED AT HIGH-LEVELS IN THE CNS IN LYME NEUROBORRELIOSIS

In patients with Lyme neuroborreliosis, inflammation and symptoms of f atigue and malaise occur out of proportion to the relatively low numbe r of spirochetes present. Previous studies have identified interleukin -6 (IL-6) as a candidate molecule for amplification of CNS inflammatio n in this disease. We pursued this possibility by measuring cytokine g ene expression by reverse-transcriptase polymerase chain reaction (RT- PCR) in the brain of rhesus macaques actively infected with Borrelia b urgdorferi. Samples of brain tissue were screened for IL-6 and interfe ron gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and captu re and ELISA readout of hybridization product. The number of copies in positive samples was then quantitated using qRT-PCR-ELISA, in which w ild-type cytokine cDNA competes with recombinant competitor DNA in the PCR. Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persiste nt infection with B burgdorferi, whereas the brains of three uninfecte d animals had undetectable levels of gene expression of these cytokine s. These data support the hypothesis that cytokines such as IL-6 are i mportant amplification molecules for CNS inflammation in Lyme neurobor reliosis.