Increased serum IL-36β and IL-36γ levels in patients with neuromyelitis optica spectrum disorders: association with disease activity

Abstract

Background Interleukin 36 (IL-36) cytokines belong to the IL-1 family and play an important role in some autoimmune diseases. However, the relationship between IL-36 and neuromyelitis optica spectrum disorders (NMOSD) remains unclear. Methods We determined serum IL-36α, IL-36β and IL-36γ levels and assessed correlations with clinical characteristics in 50 NMOSD patients and 30 healthy controls (HC). Results The concentrations of serum IL-36β and IL-36γ were significantly higher in patients with NMOSD than in HCs and decreased during remission. Serum IL-36β levels were positively correlated with the annual relapse rate (ARR), spinal cord lesion length and Expanded Disability Status Scale (EDSS) scores. Conclusions Serum IL-36β and IL-36γ levels were related to disease activity in NMOSD patients and may be important biomarkers of NMOSD.

The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

“…In recent studies, serum IL-36 agonists levels were enhanced in NMOSD patients. This study proved that IL-36γ from neutrophils could stimulate microglia to produce neutrophil-stimulating cytokines, and may contribute to neuroinflammation by promoting neutrophil-recruitment ( Song et al, 2019 ; Yang et al, 2019 ) Neutrophils played an important role in the pathological mechanisms of NMOSD, because polymerization of abnormal neutrophils was found in NMOSD lesions, and the inhibition of neutrophilic protease could attenuate AQP4-IgG damage in the mouse brain ( Yang et al, 2019 ) In addition, murine bone-marrow derived dendritic cells (BMDC) and CD4 + T lymphocytes both expressed IL-36R and responded to IL-36α ( Song et al, 2019 ) In turn, the increase of IL-36α may affect immune cells in NMOSD and cause ongoing inflammation. There was a similar cytokine milieu in the cerebrospinal fluid of NMOSD patients and in the synovial fluid of patients with RA.…”

“…There was a similar cytokine milieu in the cerebrospinal fluid of NMOSD patients and in the synovial fluid of patients with RA. Furthermore, IL-36α may locally ameliorate the effects of IL-17α and TNF-α, and contributed to the pathomechanisms of psoriasis ( Yang et al, 2019 ).…”

“…Additionally, serum IL-36 levels were positively correlated with disease severity in psoriasis ( Sehat et al, 2018 ) Besides, serum levels of IL-36α ( Song et al, 2019 ) and IL-36β ( Yang et al, 2019 ) in NMOSD patients correlated with disease severity. Thus, in the future, IL-36 may serve as a prognostic marker in partial autoimmune diseases.…”

Expression and Clinical Correlation Analysis Between Repulsive Guidance Molecule a and Neuromyelitis Optica Spectrum Disorders

“…The length of spinal lesions is correlated with inflammatory activity and neurological impairment (21,37) and is correlated with disease severity based on the admission EDSS score (38,39). Our study demonstrated for the first time that RGMa levels were positively correlated with the length of spinal lesions on NMOSD MRI scans.…”

IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore

“…Given the role of IL-36 in intestinal wound healing, it was suggested that this change in expression could result in persistent pro-inflammatory responses, leading to enterocolitis susceptibility in Hirschsprung’s disease affected infants [ 80 ]. IL-36 expression has also been observed to be altered in both myasthenia gravis and neuromyelitis optica spectrum disorder [ 81 , 82 ].These findings indicate that IL-36 may merit further investigation in brain and neurological diseases.…”