Why does tumor necrosis factor targeted therapy reactivate tuberculosis?
Treatment of chronic inflammatory conditions, such as rheumatoid arthritis and Crohn's disease, with tumor necrosis factor (TNF) targeted biologics is associated with an increased risk of infectious complications, especially tuberculosis (TB). Clinical studies have revealed that monoclonal anti-TNF antibodies (e.g., infliximab) more frequently reactivate TB than a TNF receptor p75 immunoglobulin fusion construct (etanercept). Experimental studies in mice have shown TNF to be an essential component of protective granuloma formation. Based on these studies and the known pharmacological properties of the 2 prototype TNF targeted biologic agents, this review discusses 3 hypotheses that might explain the unpredicted differential risk of infectious complications: differential induction of target cell death, differential TNF receptor signaling, and differential net inhibition of TNF bioavailability.
Ehlers
Stefan
S
Molecular Infection Biology Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany. sehlers@fz-borstel.de
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D000068800:Etanercept; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000276:immunology; D000069285:Infliximab; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012008:Recurrence; D015398:Signal Transduction; D014397:Tuberculosis, Pulmonary / Q000209:etiology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept