Effect of tumor necrosis factor-related apoptosis-inducing ligand on the reduction of joint inflammation in experimental rheumatoid arthritis.
This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA.
Jin
Cheng-Hao
CH
Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, Suwon 440-746, Korea.
Chae
Su Young
SY
Kim
Tae Hyung
TH
Yang
Han-Kwang
HK
Lee
Eun Young
EY
Song
Yeong Wook
YW
Jo
Dong-Gyu
DG
Lee
Kang Choon
KC
D000818:Animals; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D016207:Cytokines / Q000097:blood; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007596:Joints / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D019169:Jurkat Cells; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology* / Q000627:therapeutic use
D001323:Autoantibodies; D016207:Cytokines; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand