Abstract
The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with the clinical response and we monitored cytokine expression in biopsies from inflamed tissues. We evidenced a dual role of TNF-blockade. In peripheral blood, it increased the expression of cytokines such as IL-17, IL-10, and IFN-γ, and enhanced the expression of activation markers and the proliferative response of CD4 T cells to TCR stimulation. By contrast, in biopsies from target tissues, TNF-blockade diminished the expression of Th17/Th1 cytokine and early inflammatory genes. Importantly, the enhanced T cell responses to TCR-stimulation did not impair the clinical response to the therapy and, in responder patients, occurred with the concomitant down-regulation of inflammatory genes in the target tissues.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
-
Clinical Trial
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adalimumab
-
Adolescent
-
Adult
-
Aged
-
Aged, 80 and over
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
-
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Monoclonal / therapeutic use
-
Antibodies, Monoclonal, Humanized
-
Antigens, CD / genetics
-
Antigens, CD / metabolism
-
B-Lymphocytes / cytology
-
B-Lymphocytes / metabolism
-
Bacterial Toxins / immunology
-
Blood / drug effects
-
Blood / immunology*
-
Blood / metabolism
-
CD4-Positive T-Lymphocytes / cytology
-
CD4-Positive T-Lymphocytes / drug effects
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
Cell Proliferation / drug effects
-
Cytokines / blood
-
Cytokines / genetics
-
Cytokines / metabolism
-
Enterotoxins / immunology
-
Etanercept
-
Female
-
Gene Expression / drug effects
-
Gene Expression / immunology
-
Humans
-
Immunoglobulin G / pharmacology
-
Immunoglobulin G / therapeutic use
-
Inflammation / drug therapy
-
Inflammation / immunology
-
Inflammation / metabolism
-
Inflammatory Bowel Diseases / drug therapy
-
Inflammatory Bowel Diseases / immunology
-
Inflammatory Bowel Diseases / metabolism
-
Infliximab
-
Leukocytes, Mononuclear / drug effects
-
Leukocytes, Mononuclear / immunology
-
Leukocytes, Mononuclear / metabolism
-
Lymphocyte Activation / drug effects*
-
Lymphocyte Activation / immunology
-
Male
-
Middle Aged
-
Psoriasis / drug therapy*
-
Psoriasis / immunology
-
Psoriasis / metabolism
-
Receptors, Antigen, T-Cell / metabolism*
-
Receptors, Tumor Necrosis Factor / therapeutic use
-
Skin / drug effects
-
Skin / immunology*
-
Skin / metabolism
-
Superantigens / immunology
-
T-Lymphocyte Subsets / cytology
-
T-Lymphocyte Subsets / drug effects
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
-
T-Lymphocytes / cytology
-
T-Lymphocytes / drug effects*
-
T-Lymphocytes / immunology
-
T-Lymphocytes / metabolism
-
Treatment Outcome
-
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
-
Tumor Necrosis Factor-alpha / immunology
-
Viral Matrix Proteins / immunology
-
Young Adult
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Antibodies, Monoclonal
-
Antibodies, Monoclonal, Humanized
-
Antigens, CD
-
Bacterial Toxins
-
Cytokines
-
Enterotoxins
-
Immunoglobulin G
-
Receptors, Antigen, T-Cell
-
Receptors, Tumor Necrosis Factor
-
Superantigens
-
Tumor Necrosis Factor-alpha
-
Viral Matrix Proteins
-
enterotoxin F, Staphylococcal
-
Infliximab
-
Adalimumab
-
Etanercept