Background Antigen B (AgB) is a lipoprotein secreted in hydatic cyst by Echinococcus granulosus larval stage (1) and seems to be responsible to regulate immune balance via Th2 response to promotes survival of the parasite (2). A Th2 response can suppress the pro-inflammatory Th1 response generated in several immunopathologies.
Objectives To evaluate the effect of AgB in three animal models of arthritis.
Methods In all models, mice were divided into three groups: vehicle (saline) or AgB (2 and 10μg – once a day, intraperitoneal). BALB/c mice (n=21) were treated and then injected with zymosan into knee joint for development of zymosan Induced-arthritis (ZYA). Nociception in 0, 4 and 6 hours and leukocytes articular migration 6 hours after intra-articular (ia) injection were assessed. Antigen Induced-arthritis (AIA) was induced in BALB/c (n=36) with methylated bovine serum albumin (mBSA) and treatment started one day before ia injection of mBSA. Paw nociception in 0, 3, 5, 7 and 24h and neutrophils migration into knee joints 24h after ia injection of mBSA were evaluated. DBA/1J mice had Collagen Induced-arthritis (CIA) and were divided into preventive (n=25, 18 days of treatment) or therapeutic groups (n=27, 10 days of treatment starting after the onset of arthritis). In the preventive group, articular score, nociception, paw edema and body weight were evaluated. In the therapeutic group, articular score and nociception were evaluated and knee joints were collected to analyses cytokine th1/th2/th17 profile. Statistical analysis: ANOVA or Kruskal-Wallis.
Results In ZYA, both treatment reduced nociception in 4 and 6h (p<0.001) and inhibited leukocytes migration to inflammatory site (39.67±8.57, 55±13.71x104 leukocytes/cavity, respectively) compared with vehicle (159.7±39.32x104 leukocytes/cavity) (p<0.05). In AIA, both doses of AgB treatment reduced nociception at 3, 5, 7 and 24h compared with vehicle (p<0.01) and inhibited neutrophils migration (7.75±2,58, 8.99±2.18x104 neutrophils/cavity, respectively) compared with vehicle (55.93±9.79x104 neutrophils/cavity) (p<0.001). In CIA, preventive treatment improved nociception at the 2μg dose at days 14 and 18 (p<0.05) but did not improved articular score, paw edema or body weight. Therapeutic treatment did not improved articular score or reduced the nociception however the 2μg dose was able to reduce IL-6 (p<0.05) and TNF-a (p<0.05) levels, comparing with vehicle.
Conclusions Treatment with AgB significantly improved acute experimental arthritis, attenuated nociception and immune cells articular migration. On the other hand, AgB had no effect in chronic experimental arthritis, although therapeutic treatment reduced Il-6 and TNF-a levels, two important pro-inflammatory cytokines and prophylactic treatment improved nociception. We believe that the adjuvant use of AgB with a DMARD can lead to an additive effect on amelioration of immune-mediated arthritis short-term symptoms.
Oriol R. et al. Am J Trop Med Hyg. 1971; 20(4):569.
Siracusano A. et al. Exp Parasitol. 2008; 119(4):483-9.
Acknowledgements FIPE-HCPA, CAPES, CNPq
Disclosure of Interest None declared