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PMID: 15194570 Published · ppublish English Clinical Trial Journal Article Randomized Controlled Trial

Early effects of tumour necrosis factor alpha blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis.

Annals of the rheumatic diseases ·Vol. 63 ·No. 7 ·2004-07-00 ·Pages 769-73

Goedkoop AY, Kraan MC, Teunissen MB, Picavet DI, de Rie MA, Bos JD, Tak PP

Abstract

Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA). To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples. Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis. A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation. The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.

MeSH Terms
Adult Aged Antibodies, Monoclonal/therapeutic use Apoptosis Arthritis, Psoriatic/drug therapy,immunology,pathology Double-Blind Method Female Humans Immunohistochemistry In Situ Nick-End Labeling Infliximab Lymphocyte Count Macrophages/immunology Male Middle Aged Prospective Studies Psoriasis/drug therapy,immunology,pathology Skin/immunology,pathology Synovial Membrane/immunology,pathology T-Lymphocytes/immunology Time Factors Tumor Necrosis Factor-alpha/antagonists & inhibitors,immunology
Chemicals
Antibodies, Monoclonal Tumor Necrosis Factor-alpha Infliximab
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Goedkoop A Y
Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands.
Kraan M C
Teunissen M B M
Picavet D I
de Rie M A
Bos J D
Tak P P
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Article Info
Journal
Annals of the rheumatic diseases
Abbr.
Ann Rheum Dis
ISSN
0003-4967
DOI
10.1136/ard.2003.018085
Published
2004-07-00
Pages
769-73
Language
English
Region
England
NLM ID
0372355
PMCID
PMC1755073
Subset
IM
External Links
PubMed source DOI: 10.1136/ard.2003.018085 PMC Full Text View journal details
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