TNF Pathway in Psoriasis
Title: TNF inhibition rapidly down-regulates
multiple proinflammatory pathways in psoriasis plaques.
Authors: 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.
