title: Complications of TNF-α antagonists and iron homeostasis.
abstract: TNF-α is a central regulator of inflammation and its blockade downregulates other pro-inflammatory cytokines, chemokines, and growth factors. Subsequently, TNF-α antagonists are currently used in treatment regimens directed toward several inflammatory diseases. Despite a beneficial effect, the use of TNF-α antagonists is associated with an increased risk for infections and neoplasms; the basis for these complications is unclear. This cytokine also participates in iron homeostasis and the sequestration of this metal, mediated by TNF-α, is considered protective. We hypothesize that treatment with TNF-α antagonists predisposes the patient to infections and neoplasms by reversing the sequestration of host iron mediated by the cytokine and increasing available concentrations of this metal. It is recommended that patients who are to receive TNF-α antagonists be tested for iron overload and the use of these agents in those individuals with excess iron should be reconsidered. Furthermore, it is predicted that alternative attempts to treat inflammatory diseases by blocking other pivotal cytokines that also participate in iron homeostasis (e.g. IFN-γ, IL-1, and IL-6) will similarly be associated with infections and neoplastic complications.
authors: National Health and Environmental Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711, USA. ghio.andy@epa.gov
authors: Andrew J
authors: AJ
authors: Ghio
authors: Eugene D
authors: ED
authors: Weinberg
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D000068800:Etanercept; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007239:Infections / Q000209:etiology*; D007249:Inflammation / Q000188:drug therapy*; D000069285:Infliximab; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology*; D011092:Polyethylene Glycols; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C529000:golimumab; D000069285:Infliximab; D007501:Iron; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol