Abstract 2069: Effect of Retinoid on Experimental Autoimmune Myositis
Authors
N. Ohyanagi, T. Nanki, M. Ishido, T. Kubota, N. Miyasaka
Background
Th 1 cytokines have been demonstrated in the inflammatory muscle infiltrates in IIM. Retinoid is a general term for compounds which have biological activities of vitamin A. Some retinoids suppress Th1 cell differentiation and promote Th2 cell differentiation, and therefore they have been thought to have a beneficial effect on Th1 dominant diseases. It has been shown that retinoids have an inhibitory effect on collagen-induced arthritis. In this study, these investigators examined the effect of synthetic retinoid, Am80, on experimental autoimmune myositis (EAM).
Methods
To develop EAM, male 5-week-old SJL/J mice were immunized with emulsion of rabbit myosin and complete Freund’s adjuvant on days 0, 7, and 14. From day 0 to 20, Am80 (0, 0.2, 2.0 and 4.0 mg/kg) was orally administrated once a day. On day 21, the mice were sacrificed, and the quadriceps femoris muscles were harvested. To evaluate the efficacy of Am80, the histological myositis score of the quadriceps femoris muscles using H&E staining was obtained. Total RNA was prepared from the muscle specimens using RNA extraction solution, and then, expression of inflammatory cytokine mRNA was measured by quantitative RTPCR. In vitro , mouse myoblast was stimulated with TNF-α along with Am80 (0, 10-6, 10-7, 10-8 mol/l). After 24 hours, the concentrations of CCL2 (MCP-1), CCL5 (RANTES) and CX3CL1 (fractalkine) in the
culture supernatant were measured by ELISA.
Results
All the immunized mice developed myositis. Treatment with Am80 did not decrease the incidence. However, histological scores of the inflammatory changes in the quadriceps femoris muscles were significantly lowered by the treatment with Am80 (2.0 and 4.0 mg/kg) compared with controls. Expression of TNF-α and IL-1β mRNA in the quadriceps femoris muscles was very low in normal SJL/J mice but it was significantly upregulated in EAM mice. Moreover, treatment with Am80 significantly reduced the TNF-α and IL-1β mRNA expression. In vitro, culture with Am80 suppressed production of CCL2 and CCL5 by TNF-α-stimulated mouse myoblast. In contrast, CX3CL1 expression by the myoblast was not altered by Am80.
Conclusion
These results strongly suggest that Am80 has an inhibitory effect on EAM and regulates chemokine expression.
Editorial Comment
Treatment with the retinoid compound Am80 significantly reduced the TNF-α and IL-1β mRNA expression, strongly suggest that Am80 has an inhibitory effect on Experimental autoimmune myositis and regulates chemokine expression. Oral administration of Am80 (or a similar retinoid compound) is a potentially new therapeutic agent treatment of IIM; however human studies would be needed to see if the murine effect was similar to the human response.
