التفاصيل البيبلوغرافية
| العنوان: |
Etanercept ameliorates inflammation and pain in a novel mono-arthritic multi-flare model of streptococcal cell wall induced arthritis |
| المؤلفون: |
Chakravarthy, Kalyan, Faltus, Robert, Robinson, Gain, Sevilla, Raquel, Shin, John, Zielstorff, Mark, Byford, Alan, Leccese, Erica, Caniga, Michael J, Hseih, SuChun, Zhang, Shuli, Chiu, Chi-Sung, Zhang-Hoover, Jie, Moy, Lily Y, McLeod, Robbie L, Stoffregen, Dana, Zhang, Weisheng, Murtaza, Anwar, Cicmil, Milenko |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Rheumatoid arthritis, Animal models, Inflammation, Pain, von-Frey, SCW, TNF, Anti-TNF, Etanercept, Cytokines, Immunogenicity |
| الوصف: |
Background The impact of anti-TNF, corticosteroid and analgesic therapy on inflammation and pain was evaluated in a novel mono-arthritic multi-flare rat Streptococcal Cell Wall (SCW) model using Etanercept, Dexamethasone and Buprenorphine. Methods Multiple flares of arthritis were induced with an intra-articular injection of SCW in the hind ankle on day 1, followed by intravenous challenges on days 21 and 42. Inflammation and pain were monitored in the hind paws. Cytokine profiling, cell phenotyping, bioluminescence imaging and histopathological evaluation were also performed. Results Local injection of SCW caused a rapid onset of inflammation and pain in the injected ankle which resolved within 4 days (Flare 1). Intravenous injection 20 days after sensitization resulted in an increase in ankle diameter and pain, which partially resolved in 8 days (Flare 2). The subsequent intra-venous injection in the same animals 14 days after resulted in a more chronic disease with inflammation and pain persisting over a period of 10 days (Flare 3). In Flare 2, therapeutic administration of Dexamethasone inhibited paw swelling (95%; P<0.001) and pain (55%; P<0.05). Therapeutic administration of Buprenorphine inhibited pain (80%; P<0.001) without affecting paw swelling (0%). Prophylactic administration of Etanercept in Flare 2 inhibited paw swelling (≥60%; P<0.001) and pain by ≥30%. Expression of IL-1β, IL-6, MCP-1 and CINC was reduced by >50% (P<0.001). Treatment with Etanercept in Flare 3 inhibited paw swelling by 60% (P<0.001) and pain by 25%. Prior treatment with Etanercept in Flare 2 followed by re-administration in Flare 3 led to a complete loss in the efficacy of Etanercept. Systemic exposure of Etanercept corroborated with lack of efficacy. Dexamethasone inhibited inflammation and pain in both Flares 2 and 3 (P<0.001). Conclusions We established a novel multi-flare SCW arthritis model enabling drug intervention in different stages of disease. We show for the first time the evaluation of ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
http://www.biomedcentral.com/1471-2474/15/409 |
| الاتاحة: |
http://www.biomedcentral.com/1471-2474/15/409 |
| Rights: |
Copyright 2014 Chakravarthy et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.8350C1A8 |
| قاعدة البيانات: |
BASE |