A pathogenetic approach to autoimmune skin disease therapy: Psoriasis and biological drugs, unresolved issues, and future directions

Emira Ayroldi, Alessandra Bastianelli, Lorenza Cannarile, Maria Grazia Petrillo, Domenico V. Delfino, Alessandra Fierabracci

Research output: Contribution to journalArticle

Abstract

Psoriasis is a chronic inflammatory disease with a complex pathophysiology and a multigenic background. Autoimmunity and genetic hallmarks couple to confer the disease, which is characterized by chronic plaques (85-90% of all cases) and/or psoriasis arthritis (PsA), and involve the peripheral and sacroiliac joints, nails, and skeleton. Dissecting the ethiopathogenetic mechanisms of psoriasis and PsA is a major basic research challenge. One important question is whether a single inflammatory mediator can be responsible for the interactive network that forms between immune cells and cytokines in this disease. Despite much progress, no research has yet been able to define a single model to explain the multifaceted pathogenesis of psoriasis and PsA. It is known that both the innate and adaptive immune systems are involved, antigen presenting cells and T lymphocytes play a prominent role, and that the deregulation of the T helper (Th)-1/Th-2/Th-17/Th-23 axis is directly implicated in disease pathogenesis. Pharmacological therapy for psoriasis has evolved with the development of human knowledge of the disease pathophysiology. Thus, the first "ethiopathogenetic" drugs (e.g., methotrexate, cyclosporin, and alefacept) inhibited T-cell activation directly or targeted co-accessory molecules implicated in T-cell activation. When the mechanism underlying psoriatic inflammation was accepted as a cytokine network disorder, more specific biologics were studied in murine models and were later used clinically. Tumor necrosis factor was the first successful target of cytokine inhibition therapy for psoriasis and PsA (e.g., infliximab, adalimumab, and etanercept). With the recently discovered role for Th-17 in autoimmunity, drugs targeting interleukin-23 (ustekinumab) have become accepted for the pharmacological treatment of psoriasis. The expansion of pharmacological treatment options for psoriasis is not complete. As the knowledge of pathogenetic mechanisms increases, it may be possible to design therapeutic approaches that selectively target the ethiopathogenetic cells or cytokines while sparing the others. In this way, using a more targeted drug therapy may preserve the integrity of the immune system. Thus, one great struggle in treating this complex disease is the challenge to synthesize the "perfect" drug.

Original languageEnglish
Pages (from-to)3176-3190
Number of pages15
JournalCurrent Pharmaceutical Design
Volume17
Issue number29
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Biological Therapy
Psoriasis
Skin Diseases
Autoimmune Diseases
Pharmaceutical Preparations
Arthritis
Cytokines
Pharmacology
Autoimmunity
T-Lymphocytes
Immune System
Direction compound
Interleukin-23
Therapeutics
Sacroiliac Joint
Human Development
Antigen-Presenting Cells
Drug Delivery Systems
Nails
Biological Products

Keywords

  • Autoimmunity
  • Biological therapy
  • IL-12/IL-23 antagonists
  • Inflammation
  • Keratinocyte proliferation/differentiation
  • Psoriasis
  • Psoriasis arthritis
  • T-helper differentiation
  • TNF-aantagonists

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

A pathogenetic approach to autoimmune skin disease therapy : Psoriasis and biological drugs, unresolved issues, and future directions. / Ayroldi, Emira; Bastianelli, Alessandra; Cannarile, Lorenza; Petrillo, Maria Grazia; Delfino, Domenico V.; Fierabracci, Alessandra.

In: Current Pharmaceutical Design, Vol. 17, No. 29, 10.2011, p. 3176-3190.

Research output: Contribution to journalArticle

Ayroldi, Emira ; Bastianelli, Alessandra ; Cannarile, Lorenza ; Petrillo, Maria Grazia ; Delfino, Domenico V. ; Fierabracci, Alessandra. / A pathogenetic approach to autoimmune skin disease therapy : Psoriasis and biological drugs, unresolved issues, and future directions. In: Current Pharmaceutical Design. 2011 ; Vol. 17, No. 29. pp. 3176-3190.
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