Neuroimmune expression in hip osteoarthritis: a systematic review

Manuel Ribeiro da Silva, Daniela Linhares, Daniel Marques Vasconcelos, Cecilia Juliana Alves, Nuno Neves, Gilberto Costa, Meriem Lamghari

Neuroimmune axis is central in the physiopathology of hip osteoarthritis (OA), but its specific pathways are still unclear. This systematic review aims to assess the nervous and immune system profile of patients with hip osteoarthritis (OA) when compared to healthy controls. A systematic review followed PRISMA guidelines was conducted. A two-step selection process was completed, and from 609 references 17 were included. The inclusion criteria were: original articles on adult patients with hip OA, with assessment of neuroimmune expression. Articles with other interventions prior to analysis and those without a control group were excluded. Thirty-nine relevant neuroimmune markers were identified, with assessments in bone, cartilage, synovial membrane, synovial fluid, whole blood, serum and/or immune cells. GM-CSF, IFN-γ, IL-1α, IL-6, IL-8, IL-1 and TNF-α presented variable expression among tissues studied when compared between hip OA and controls. VEGFs and TGF-ß isoforms showed similar tendencies among tissues and studies. On nervous expression, CGRP, Tuj-1 and SP were increased in synovial membrane. Overall, patients with hip OA presented a higher number of overexpressed markers. For the first time a systematic review on neuroimmune expression in patients with hip OA found an upregulation of neuroimmune markers, with deregulated balance between pro and anti-inflammatory cytokines. However, no clear systematic pattern was found, and few information is available on nervous expression. This highlights the importance of future research with clear methodologies to guide the management of these patients.