title: Infections and biological therapy in rheumatoid arthritis.
abstract: Infections are common in patients with rheumatic disorders. Reasons for such vulnerability include alterations of immunoregulation, disease severity, debility, co-morbid illnesses and the use of immunosuppressive medications. The advent of new biological agents has precipitated a further examination of the links between infection, the underlying disease and its treatment, resulting in several interesting observations. Interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-alpha), the major pro-inflammatory cytokines, play important roles in host defence against infection. Inhibition of their activity could therefore be anticipated to augment the risk of infection in patients with pre-existing abnormalities of immune regulation. Slight increases in the rates of infection were noted in the clinical trials of IL-1 receptor antagonist (IL-1Ra). In addition, a small number of opportunistic infections have been observed with the TNF inhibitor, etanercept. However, a marked increase in opportunistic infection, particularly tuberculosis, has occurred with the use of infliximab, an agent that also blocks TNF activity. The precise mechanisms by which these agents predispose to infection are currently being explored. The answers are likely to add significantly to our knowledge of how immune dysfunction contributes both to the pathophysiology of disease and the complications of therapy.
authors.affiliation: Department of Rheumatology, University of Leeds, Leeds General Infirmary, Leeds LS1 3EX, UK. g.cunnane@leeds.ac.uk
authors.forename: Gaye
authors.initials: G
authors.lastname: Cunnane
authors.forename: Michele
authors.initials: M
authors.lastname: Doran
authors.forename: Barry
authors.initials: B
authors.lastname: Bresnihan
mesh_terms: D000068879:Adalimumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007239:Infections / Q000209:etiology* / Q000276:immunology; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept