Effects of a low-dose IL-2 treatment in HLA-B27 transgenic rat model of spondyloarthritis

• Published in: Arthritis research & therapy 2021-07, Vol.23 (1), p.193-193, Article 193
• Main Authors: Araujo, L M, Jouhault, Q, Fert, I, Bouiller, I, Chiocchia, G, Breban, M
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Arthritis; Care and treatment; Cloning; Complications and side effects; Cytokines; Diarrhea; Disease; Ecology, environment; Experiments; Genetic aspects; Health; Histology; HLA-B27 Antigen - genetics; HLA-B27 transgenic rat; Humans; Inflammatory bowel disease; Interleukin-2 - therapeutic use; Life Sciences; Low-dose IL-2; Lupus; Lymphocytes; Pathogenesis; Proteins; Psoriasis; Rats; Rats, Transgenic; Regulatory T cells; Rheumatoid arthritis; Spleen; Spondylarthritis - drug therapy; Spondylarthritis - genetics; Spondyloarthritis; Spondyloarthropathies; T cells; T-Lymphocytes, Regulatory; Variance analysis
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-021-02559-y

HLA-B27/human β2m transgenic rats (B27-rats) develop an inflammatory disorder resembling spondyloarthritis (SpA) with dysregulated IL-10/IL-17 production by regulatory T cells (Treg). Treg plays a major role in controlling pathogenic inflammatory processes. Interleukin 2 (IL-2), a cytokine which promotes Treg cell survival and function, may thus have therapeutic efficacy in SpA. Here, we tested this hypothesis using a low dose of IL-2 treatment in B27-rat. B27-rats aged 4 weeks (before disease onset) and nontransgenic (NTG) littermates were administered intraperitoneally recombinant human IL-2 (Sanofi®; 2,000IU/injection) or PBS, 3 days per week during 6 weeks. Assessment of treatment effect was performed, based on clinical (weight, diarrhea, arthritis), histological (proximal and distal colon, caecum, ileum and tarsal/ankle joint) scores, and frequency of Treg in the spleen and lymph nodes (LN). IL-2 administration had no effect on weight gain, either in B27- or NTG-rats. Over the 6 weeks of treatment, the clinical disease score worsened similarly in both IL-2-treated and control groups of B27-rats. The macroscopic and histological evaluation of gut and joints showed marked inflammation in B27-rats; however, no change related to IL-2 treatment was observed. In the B27-rats, the percentage of Treg was moderately increased after IL-2 treatment in the spleen, but neither in mesenteric nor peripheral LN in those rats. Our data demonstrate that a low dose of IL-2 administered before disease onset was moderately effective for boosting Treg but failed to prevent SpA development in B27-rat.