Background Antigen B (AgB) is a protein secreted by Echinococcus granulosus larval stage (1) and seems to be responsible for immuneregulation via Th2 response (2). response to promotes survival of the parasite (2,3). A Th2 response can suppress the pro-inflammatory Th1 response generated in several immunopathology (2), providing therapeutic potential in autoimmune diseases.
Objectives To evaluate the effect of AgB in antigen-induced arthritis (AIA), zymosan-induced arthritis (ZYA) and collagen-induced arthritis (CIA) models.
Methods In all models, mice were divided intro three groups: vehicle (saline) and AgB (2 and 10mg – once a day). BALB/c mice (n=21) were treated with AgB and then injected with zymosan into intraarticular knee joint for ZYA. Nociception was assessed in 0, 4 and 6 h and leukocytes migration analyzed 6h after intraarticular injection. AIA was induced in BALB/c mice (n=36) with methylated bovine serum albumin (mBSA) and AgB treatment started one day before intraarticular mBSA injection. Nociception was evaluated in 0, 3, 5, 7 and 24h and neutrophils migration into knee joints was evaluated 24h after intraarticular mBSA injection CIA was induced in DBA/1J mice (n=27) with bovine collagen type II and were monitored daily for arthritis, AgB treatment starting after onset of disease and lasting for 10 days. Articular score and nociception were evaluated and knee joints were collected to analyze the cytokine (CBA th1/th2/th17). Statistical analysis was assessed with ANOVA.
Results In ZYA, both dose treatment reduced nociception in 4 and 6 h (p<0.001) and inhibited leukocytes migration (39.67±8.57x104 and 55±13.71x104 leukocytes/cavity, respectively) compared with vehicle (159.7±39.32x104 leukocytes/cavity) (p<0.05). In AIA, both doses of AgB reduced nociception at 3, 5, 7 and 24h compared with vehicle (p<0.01) and inhibited neutrophils migration (7.75±2,58x104 and 8.99±2.18x104 neutrophils/cavity, respectively) compared with vehicle (55.93±9.79x104 neutrophils/cavity) (p<0.001). AgB treatment in CIA did not improved clinical score or reduced nociception, but the 2mg dose was able to reduce IL-6 (p<0.05) and TNF-a (p<0.05) levels.
Conclusions Treatment with AgB improved acute experimental arthritis attenuating nociception and cells migration to the joint. Although AgB had no effect on nociception and clinical score in chronic arthritis, it was able to reduce IL-6 and TNF-a levels, two important pro-inflammatory cytokines. We believe that a prophylactic intervention or the adjuvant use of AgB can attenuate joint damage and nociception also in chronic arthritis.
Oriol R, Williams JF, Esandi MVP, Oriol C. Purification of lipoprotein antigens of Echinococcus granulosus from sheep hydatid fluid. American Journal of Tropical Medicine and Hygiene. 1971;20(4):569;
Siracusano A, Rigano R, Ortona E, Profumo E, Margutti P, Buttari B, et al. Immunomodulatory mechanisms during Echinococcus granulosus infection. Experimental Parasitology. 2008;119(4):483-9.
Disclosure of Interest None declared