Adalimumab, a fully human anti-TNF-alpha monoclonal antibody, treatment does not influence experimental UV response in the skin of rheumatoid arthritis patients.
TNF-alpha is known to play an important role in UV-induced immunomodulation and photodamage. It plays a role in UVB-mediated induction of apoptosis and is a strong inducer of the c-Jun N-terminal kinase (JNK) pathway, which eventually leads to the loss of dermal collagen and elastin content. Recently chimeric anti-TNF-alpha has been introduced as a therapy for rheumatoid arthritis. The aim of the present study was to investigate the effect of anti-TNF-alpha treatment on UV-induced DNA damage, apoptosis, and induction of matrix metallo proteinases. Twelve patients with rheumatoid arthritis were included and irradiated with 2 MED broadband UVB before and after administration of 0.5 mg/kg anti-TNF-alpha monoclonal antibody. Twenty-four hours after irradiation biopsies were taken. Frozen and paraffin sections were stained for p53, c-Jun, phosphorylated c-Jun, sunburn cells and MMP-1. No significant changes were observed in the expression of p53 and sunburn cells and MMP-1 content after treatment with anti-TNF-alpha, whereas a slight but significant decrease in c-Jun and phosphorylated c-Jun expression was noted (P = 0.0250 and P = 0.0431, respectively). Our results showed no influence of anti-TNF-alpha on UV response at therapeutic doses in patients with rheumatoid arthritis.
Tjioe
M
M
Department of Dermatology University Medical Center Nijmegen, the Netherlands.
Gerritsen
M J P
MJ
Den Broeder
A A
AA
Van Hooijdonk
C A E M
CA
Kroot
E J A
EJ
Van Riel
P L C M
PL
Barrera
P
P
Van De Kerkhof
P C M
PC
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004249:DNA Damage; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects*; D013471:Sunburn / Q000209:etiology / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; D000068879:Adalimumab