TNF Pathway in Psoriasis

Title: TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques.
: Gottlieb AB, et al.
Publication: J Immunol. 2005 Aug 15;175(4):2721-9.

The authors wanted to elucidate the mechanism of tumor necrosis factor (TNF)-inhibiting drugs in skin diseases that create lesions, such as psoriasis. To do this, they enrolled 10 patients with psoriasis treated for 6 months. They evaluated the histological response (microscopic structure of the tissues and organs), expression of genes involved in inflammation, and cellular infiltration in psoriatic plaques.

The authors found:

  • Rapid and complete reduction of Interleukin or (IL)-1 and IL-8 (immediate/early genes)
  • Followed by progressive reduction in other inflammation-related genes
  • Slower reduction in infiltrating myeloid cells (CD11c+ cells) and T-lymphocytes (or T cells)

Decreased infiltrations of the following cells are caused by reduction of these mRNA levels:

Decreased infiltration rate Decreased mRNA levels
Neutrophils (a type of granular white blood cell that destroys microorganisms) IL-8 mRNA
T lymphocytes IFN-gamma-inducible protein-10 (CXCL10) mRNA
Dendritic cells MIP-3 alpha (CCL20) mRNA

Dendritic cells seem to be less activated with therapy, suggested by reduced levels of :

  • IL-23 mRNA
  • inducible NO synthase mRNA and protein.

Decreased dendritic cell-mediated T-cell activation, in turn, can decrease the T cell inflammatory gene expression and the number of T cells.

The authors suggested that etanercept-induced inhibition of TNF/lymphotoxin works by stopping the activation and maturation of dendritic cells, subsequent T-cell activation, and production of a chemical cascade (including substances produced by various cells) that trigger the aberrant immune system response in psoriasis.

Thus, the drug can reverse the hyperplasia or abnormal enlargement of tissue, as well as skin inflammation in psoriatic plaque.

Editor’s Note: cellular infiltration is the abnormal migration of cells from their original location into another organ or tissue, as result of unusual growth and multiplication.

Myeloid cells are cells of the bone marrow. T-lymphocytes are a subset of white blood cells that develop in the thymus and orchestrate the immune system’s response to infected or malignant cells.

mRNA or messenger RNA is a nucleic acid intermediate used in production of proteins.

Dendritic cells are immune system cells, named because they have projections like nerve dendrites. These cells attract antigens (substances that elicit an immune response) and present them to activate T cells.

Lymphotoxin is a lymphokine (substance released by T-cell) that is toxic to susceptible target cells.

Main Menu
Health Articles
Health News
Health Research
Site Map

Health Conditions
Cardiovascular Health
Digestive Health
Infectous Diseases
Musculoskeletal Health
Pregnancy & Childbirth
Skin Health

Misc. Health Articles
Presidential Diseases

Medical Research

Psoriasis Overview
Psoriasis Pictures
Research Summaries

©copyright 2004 - Health In Plain English. All Rights Reserved.

Health Articles Health News Health Research Explained in Plain English