FRI0297 Role of serum interleukin-6 in blood brain barrier damages in neuropsychiatric systemic lupus erythematosus

Background Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. We have recently demonstrated that the breakdown of blood brain barrier (BBB) plays a crucial role in the development of diffuse psychiatric/neuropsychological manifestations (diffuse NPSLE), allowing influx of neuron-reactive autoantibodies from systemic circulation into the brain. However, the mechanism of BBB damages remains unclear. On the other hand, although CSF interleukin-6 (IL-6) has been shown to be elevated in NPSLE, there has been no report on serum IL-6 in NPSLE. Objectives The present study was designed in order to elucidate the roles of serum IL-6 in the pathogenesis, especially in development of BBB damages, In NPSLE. Methods Paired serum and cerebrospinal fluid (CSF) samples were obtained from 101 SLE patients when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral nervous system involvement [focal NPSLE]) and from 22 non-SLE control patients with non-inflammatory neurological diseases. The levels of albumin and IL-6 in CSF and sera were measured by ELISA. Results Serum IL-6 as well as CSF IL-6 was significantly elevated in acute confusional state (ACS) compared with non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or focal NPSLE (figure). Q albumin (CSF/serum albumin quotient) was also significantly higher in ACS than in the other 2 groups of NPSLE. Of note, serum IL-6 (r=0.2801, p=0.0207), but not CSF IL-6 (r=0.1602, p=0.1918), was significantly correlated with Q albumin in patients with diffuse NPSLE, including ACS and non-ACS, although serum IL-6 was significantly correlated with CSF IL-6 in this population (r=0.3205, p=0.082). Conclusions These results indicate that serum IL-6 as well as IL-6 is involved in the pathogenesis of NPSLE. The data also confirm that the severity of BBB damages plays a crucial role in the development of ACS, the severest form of diffuse NPSLE. Finally, it is suggested that serum IL-6 might play a most important role in BBB breakdown in NPSLE, whereas CSF IL-6 might be involved in subsequent central nervous system inflammation. Disclosure of Interest None declared