. Author manuscript; available in PMC: 2021 Apr 6.

Published in final edited form as: Nat Rev Rheumatol. 2019 Mar;15(3):137–152. doi: 10.1038/s41584-018-0156-8

Table 4 |.

Cytokines in NPSLE

Cytokine	Effects	Refs
TNF	Conflicting data regarding elevated CSF levels in NPSLE Treatment with TNF inhibitors can induce SLE-like symptoms Increased levels can impair the BBB via increased local inflammation	^{115,211–214}
BAFF	Mediates B cell survival and promotes immunoglobulin class switching (important in SLE pathogenesis) Anti-BAFF (belimumab) antibody treatment is approved for the treatment of SLE, but efficacy in NPSLE has not been established	^215,216,189
IFNα	Important in SLE pathogenesis Strong systemic interferon signature in patients with NPSLE Induced in vitro by CSF from patients with NPSLE Activates microglia leading to synaptic pruning Can induce depression (most common adverse effect), psychotic features, confusion, focal neurological deficits and seizures	^{149–151,217–219}
TWEAK	Mediates BBB disruption, choroid plexus cellular infiltration and neuronal damage Elevated in the CSF of patients with SLE	^49,156,220
IFNγ	Mainly produced by T cells and found in high levels in sera from patients with SLE Elevated in the CSF of patients with NPSLE, which can distinguish NPSLE from demyelinating neurological conditions	¹⁶⁰
IL-6	Secreted primarily by myeloid cells, activated astrocytes and endothelial cells Stimulates B cells, promotes immunoglobulin secretion by plasma cells, promotes differentiation of T_H17 cells and inhibits differentiation of regulatory T cells Elevated in the CSF of patients with NPSLE, but similarly elevated in CSF from patients with demyelinating neurological conditions and septic meningitis	^{152,160,211,221}
IL-8	Secreted by several cell types, including activated endothelial cells Elevated in the CSF of patients with NPSLE, but similarly elevated in CSF from patients with demyelinating neurological conditions and septic meningitis	^152,160,211

BAFF, B cell activating factor; BBB, blood–brain barrier; CSF, cerebrospinal fluid; NPSLE, neuropsychiatric systemic lupus erythematosus; SLE, systemic lupus erythematosus; T_H17 cell, T helper 17 cell; TWEAK, TNF-like weak inducer of apoptosis.