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Resolution of endothelial activation and down-regulation of Tie2 receptor in psoriatic skin after infliximab therapy - 09/08/11

Doi : 10.1016/j.jaad.2006.01.038 
Trevor Markham, MD a, Ronan Mullan, MRCP a, Lucy Golden-Mason, PhD c, Sarah Rogers, MD b, Barry Bresnihan, MD a, Oliver FitzGerald, MD a, Ursula Fearon, PhD a, Douglas J. Veale, MD a,
a From the Departments of Rheumatology 
b Dermatology 
c National Liver Transplant Unit, St Vincent’s University Hospital and Conway Institute of Molecular Medicine 

Reprint requests: Douglas J. Veale, MD, Department of Rheumatology, St Vincent’s University Hospital, Dublin 4, Ireland.

Dublin, Ireland

Abstract

Background

Psoriasis is a common dermatosis characterized by erythematous skin plaques and associated arthritis. Microvessels of the papillary dermis in psoriatic lesions are elongated, tortuous, and dilated, which contributes significantly to the proinflammatory response. Angiopoietin (Ang) 1 and 2 and their receptor, Tie2, are a family of growth factors recognized in inflammatory lesions to be critical for new blood vessel growth and maintenance, with recent studies suggesting tumor necrosis factor (TNF)-⍺-induced angiogenesis is in part mediated by the Tie2 receptor. The aim of this study was to evaluate the effect of anti-TNF-⍺ therapy on angiogenic growth factor expression and on the cellular infiltrate in psoriatic lesional skin.

Methods

Sixteen patients with moderate to severe psoriasis and associated psoriatic arthritis (n = 13) received infliximab infusions (3-5 mg/kg) at baseline and at 2 and 6 weeks. Clinical assessments and skin biopsies were undertaken at baseline, and at 2 and 12 weeks. Ang 1, Ang 2, Tie2, and TNF-⍺ messenger RNA expression were quantified by real-time polymerase chain reaction. Protein expression of vascular endothelial growth factor, Ang 2, Tie2, TNF-⍺, and the inflammatory infiltrate was determined using immunohistology. We conducted clinical assessments including Psoriasis Area and Severity Index, percentage body surface area, Arthritis Disease Activity Score, and Health Assessment Questionnaire.

Results

At baseline expression of Ang 1/2, vascular endothelial growth factor, Tie2, and TNF-⍺ messenger RNA and protein were greater in preinvolved skin compared with uninvolved skin (P < .05). Infliximab produced a significant reduction in protein expression of Ang 2, vascular endothelial growth factor, and Tie2 (P < .001) along with a decrease in messenger RNA expression of Ang 1 (P < .045) and Tie2 (P < .021). This was paralleled by a significant reduction in the inflammatory infiltrate scores (P < .001) and platelet-endothelial cell adhesion molecule (CD31) expression (P = .001), suggesting deactivation of endothelial cell. There was a 93% mean reduction in Psoriasis Area and Severity Index (P = .001), and a significant reduction in Disease Activity Score 28 (P = .012) and mean Health Assessment Questionnaire scores by week 12.

Limitations

This study involves a small number of patients.

Conclusion

These results suggest infliximab is both effective and well tolerated in severe psoriasis, resulting in deactivation of endothelium and down-regulation of growth factor and cytokine expression, leading to a decrease in the cellular infiltrate and clinical improvement in psoriasis. Furthermore, the effect of infliximab on growth factor expression, in particular Tie2, supports previous in vitro work suggesting TNF-⍺ may be a major regulator of the Ang/Tie2 pathway.

Le texte complet de cet article est disponible en PDF.

Abbreviations used : Ang, BSA, DAS-28, EC, HAQ, mRNA, PASI, PCR, PECAM, PsA, TNF, VEGF


Plan


 Supported by a grant from the Health Research Board of Ireland.
Conflicts of interest: None identified.
Presented and published at the British Association of Dermatologists 2003 Annual Meeting in Brighton, United Kingdom [Presented July 1, 2003; published Br J Dermatol 2003;149(suppl):20] and American College of Rheumatologists 2003 Annual Meeting in Orlando, Florida [Presented October 23, 2003; published Arthritis Rheum 2003;48(Suppl):s168].


© 2006  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 54 - N° 6

P. 1003-1012 - juin 2006 Retour au numéro
Article précédent Article précédent
  • Altered keratin 17 peptide ligands inhibit in vitro proliferation of keratinocytes and T cells isolated from patients with psoriasis
  • Zhu Shen, Ling Chen, Yu-F. Liu, Tian-W. Gao, Gang Wang, Xue-L. Fan, Jian-Y. Fan, Ping-S. Fan, Chun-Y. Li, Bin Liu, Yu-P. Dang, Cheng-X. Li
| Article suivant Article suivant
  • Methotrexate plus narrowband UVB phototherapy versus narrowband UVB phototherapy alone in the treatment of plaque-type psoriasis: A randomized, placebo-controlled study
  • Pravit Asawanonda, Yaowalak Nateetongrungsak

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