How tumour necrosis factor blockers interfere with tuberculosis immunity.
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.
Harris
J
J
Adjuvant Research Group, School of Biochemistry and Immunology, and St. James's Hospital, Trinity College Dublin, Dublin, Ireland. jaharris@tcd.i.e
Keane
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy; D001343:Autophagy / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D004198:Disease Susceptibility; D000068800:Etanercept; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000009:adverse effects / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D010588:Phagosomes / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept