Exploring the involvement of NLRP3 and Il-1β in Osteoarthritis of the Hand: Results from a Pilot Study

Antonella Fioravanti, Sara Tenti, Megan McAllister, Melody El Chemaly, Amanda Eakin, Joseph McLaughlin, AJ Bjourson, Elena Frati, V. E. McGilligan, David Gibson, Sara Cheleschi

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Abstract

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin (IL)-1β plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multi-protein complexes, named inflammasomes for its activation.
The aim of this study was to investigate the involvement of IL-1β and the NLRP3 inflammasome in patients with EHOA and non-erosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1β and NLRP3, the serum levels of IL-1β, IL-6, IL-17 and Tumor Necrosis Factor (TNF)-α and the protein levels of IL-1β and NLRP3. We also assessed the relationships between IL-1β and NLRP3 and clinical, laboratory and radiological findings.
Fifty-four patients with HOA (25 EHOA, 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cells (PBMCs) gene and protein expression of IL-1β and NLRP3 was quantified by quantitative real-time PCR and western blot. IL-1β, IL-6, IL-17 and TNF-α serum levels were determined by ELISA.
IL-1β gene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in NEHOA group versus control (p=0.0063) and EHOA groups (p=0.0038). IL-1β serum levels weren’t significantly different across the groups; IL-6, IL-17 and TNF-α weren’t detectable in any sample. IL-1β concentrations were negatively correlated with Kellgren-Lawrence score in the whole population (r= -0.446; p=0.0008) and in NEHOA (r= -0.608; p=0.004), while IL-1β gene expression was positively correlated with the number of joint swellings in EHOA group (r=0.512; p=0.011).
Taken together, our results, showing poorly detectable IL-1β concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at local level.
Original languageEnglish
Article number2363460
Number of pages13
JournalMediators of Inflammation
DOIs
Publication statusPublished - 10 Mar 2019

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