Abstract
Tumour necrosis factor (TNF) is a potent inflammatory cytokine that plays an important role in immunity to numerous bacterial infections, including Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) in humans. Infliximab, adalimumab, certolizumab pegol and etanercept are anti-TNF agents used to treat a range of inflammatory/autoimmune diseases, such as rheumatoid arthritis. The use of some of these drugs has been linked to reactivation TB. In addition to blocking TNF-mediated immune responses, some anti-TNF drugs have been found to interfere with innate immune responses, such as phagolysosomal maturation and monocyte apoptosis, as well as cell-mediated responses, including interferon-gamma secretion by memory T cells, complement-mediated lysis of Mtb-reactive CD8+ T cells and increased regulatory T cell activity. This review summarizes some of the reported effects of TNF blockers on immune cell responses in the context of the observed clinical data on TB reactivation in patients on anti-TNF therapy.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / pharmacology
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Apoptosis / drug effects
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Autoimmune Diseases / complications
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Autoimmune Diseases / drug therapy
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Autophagy / drug effects
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Dendritic Cells / drug effects
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Disease Susceptibility
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Etanercept
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Humans
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Immunity, Cellular / drug effects
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Immunoglobulin G / adverse effects
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Immunoglobulin G / pharmacology
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Immunosuppressive Agents / adverse effects
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Immunosuppressive Agents / pharmacology*
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Inflammation / complications
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Inflammation / drug therapy
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Lymphocyte Activation / drug effects
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Macrophage Activation / drug effects
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Mice
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / immunology
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Phagosomes / drug effects
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Receptors, Tumor Necrosis Factor
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T-Lymphocyte Subsets / drug effects
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Tuberculosis / immunology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / physiology
Substances
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Antibodies, Monoclonal
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Immunoglobulin G
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Immunosuppressive Agents
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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Etanercept