Thalidomide upregulates macrophage inflammatory protein-1? in a herpes simplex virus-induced Beh�et?s disease-like animal model

Abstract

The mechanism of action of thalidomide in the treatment of patients with Behc¸et's disease (BD) is poorly understood. There is some evidence to suggest that certain immunological abnormalities are associated with the pathogenesis of BD. A BD-like mouse model induced by herpes simplex virus (HSV) inoculation shows similar immunological abnormalities. In this study, thalidomide was administered in order to understand the mechanism for the improvement in symptoms in BD-like mice. Eight out of ten thalidomide-treated mice showed improvement but none of ten placebotreated mice (P<0.005). The improvements were seen in mucocutaneous symptoms. The mice were sacrificed on the 6th day, and the spleens subjected to RT-PCR, FACS, Western blot and immunohistochemical analysis. IL-2, IL-4, IL-6, IL-10, IFN-c, TNFa, TGFb, MCP-1, RANTES, perforin, IP-10, FasL, FasR and MIP-1a were determined. Among these, TNFa, MIP-1a, perforin and Fas were influenced by thalidomide treatment. These results suggest that thalidomide can attenuate HSV-induced BD-like symptoms in mice through the downregulation of TNFa (P<0.005) and the upregulation of MIP-1a (P<0.005), perforin (P<0.05) and FasR (P<0.1).

Synthesized pyridine compound derivatives decreased TNF alpha and adhesion molecules and ameliorated HSV-induced inflammation in a mouse model

“…Taken together, these findings indicate that the decrease in MCP-1 in response to treatment with SK compounds may contribute to the amelioration of Behcet's disease symptoms. Thalidomide has been shown to effectively improve symptoms in Behcet's disease patients (Direskeneli et al, 2008) and mice (Lee et al, 2004). In the present study, the change in the severity score of SK94 treated Behcet's disease mice was similar to that of the thalidomide treated group.…”

“…Additionally, SK126 more efficiently down-regulated the serum level of TNFα, soluble ICAM-1 (sICAM-1), and soluble E-selectin (sE-selectin) when compared to thalidomide in Behcet's disease mice. Thalidomide is known to be a TNFα inhibitor (Schmidt et al, 1996) that is effective in Behcet's disease patients (Hamuryudan et al, 1998) and Behcet's disease mice (Lee et al, 2004).…”

“…In addition, SK126 more efficiently downregulated TNFα when compared to the thalidomide administered group (24.6 ± 13.9 pg/ml) (P = 0.02). Thalidomide is highly effective at suppressing oral and genital manifestations of Behcet's disease patients (Bang, 1997) and Behcet's disease mice (Lee et al, 2004); however, SK126 more effectively down-regulated the serum level of TNFα than thalidomide in Behcet's disease mice (Fig. 4).…”

Behcet’s disease: from heat shock proteins to infections

“…In a study by Sohn et al, designed to determine the possible role of immune regulation in the development of BD-like symptoms, HSV-induced ICR mice were used successfully as animal models of BD [110]. There are also many other reports of using HSV-induced BD mice as animal models [111][112][113][114][115][116][117][118]. HSV-1 gene fragments in the peripheral blood mononuclear cells of BD patients were demonstrated by in situ DNA-RNA hybridization [119].…”

Animal Models in Behçet's Disease

“…In another study, thalidomide was administered in order to understand the mechanism for the improvement in symptoms in BD-like mice [48]. Despite its inherent teratogenic risk, thalidomide has proven to be of clinical use in a small number of immunological disease, including BD [49].…”