Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Abstract

During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

“…Neuroinflammation is accompanied by BBB disturbances, allowing the influx of inflammatory cells and tissuedestructive products [50]. Moreover, inflammatory cytokines are elevated in both serum and CNS [50]. Given that the role of the BCSFB in infiltration of leukocytes during neuroinflammation is understudied and might be underestimated, we summarize the current knowledge on this topic with a focus on meningitis and MS, to highlight possible shortcomings.…”

“…SIRS includes sepsis, which is a well-known peripheral inflammatory disease. However, peripheral immune activation also occurs in autoimmune diseases, such as joint inflammation in rheumatoid arthritis, as well as in metabolic disorders, such as diabetes and obesity [36,50]. In addition, systemic inflammation is starting to be recognized as a prominent feature of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases [51].…”

“…Neuroinflammation is accompanied by BBB disturbances, allowing the influx of inflammatory cells and tissuedestructive products [50]. Moreover, inflammatory cytokines are elevated in both serum and CNS [50].…”

“…Neuroinflammation CNS inflammation has numerous causes, including bacterial infections and MS [50]. Neuroinflammation is accompanied by BBB disturbances, allowing the influx of inflammatory cells and tissuedestructive products [50].…”

Síndrome de intestino irritable y autoinmunidad

“…Por otra parte, en los últimos años la inflamación se ha considerado un factor importante en el trastorno bipolar 53 . Se ha sugerido que la inflamación periférica se asocia con incremento de inflamación en el SNC 54 , probablemente mediada por citocinas circulantes en el plasma que alteran la función de la barrera hematoencefálica 55 . Basado en lo anterior, Liu, et al, hipotetizaron que una historia de SII podría incrementar el riesgo de trastorno bipolar.…”