Cytokine & Growth Factor Reviews 13 (2002) 299–313 Survey Cytokines and anti-cytokine biologicals in autoimmunity: present and future Evangelos T. Andreakos ∗ , Brian M. Foxwell, Fionula M. Brennan, Ravinder N. Maini, Marc Feldmann Faculty of Medicine, Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK Abstract The increasing understanding of the role of cytokines in autoimmunity, and the observation that tumour necrosis factor  (TNF) is central to the inflammatory and destructive process common to several human autoimmune diseases, has led to a new generation of therapeutics, the TNF blocking agents. In this article, we review the current knowledge of the role of cytokines in autoimmunity as unravelled by studies both in the laboratory and the clinic. In addition, we discuss future prospects of the anti-TNF therapy that may involve combination therapy with other anti-cytokine or anti-T cell biologicals, or the use of small chemicals targeting molecules involved in TNF production such as NF-B and p38 MAPK. The future developments of anti-TNF and anti-cytokine therapy in general will be interesting. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Autoimmunity; Rheumatoid arthritis; Cytokine; TNF; NF-B Contents 1. Introduction ............................................................................... 299 2. Initiation, perpetuation and tissue damage in autoimmune disease .............................. 300 3. The cytokine system in rheumatoid arthritis .................................................. 300 4. The cytokine system in other autoimmune diseases ........................................... 302 5. Anti-cytokine therapy in rheumatoid arthritis ................................................. 302 6. Anti-cytokine therapy in other autoimmune diseases .......................................... 305 7. Anti-inflammatory cytokine therapy in autoimmunity ......................................... 306 8. Future prospects ........................................................................... 307 9. Conclusions ............................................................................... 308 Acknowledgements ........................................................................... 309 References ................................................................................... 309 1. Introduction Autoimmune diseases involve the activation of self-reactive T and B cells and the generation of cell-mediated and humoral immune responses against self-antigens. A large number of autoimmune diseases have been described, ∗ Corresponding author. Tel.: +44-20-8383-4444; fax: +44-20-8383-4499. E-mail addresses: evangelos.andreakos@ic.ac.uk (E.T. Andreakos), b.foxwell@ic.ac.uk (B.M. Foxwell), f.brennan@ic.ac.uk (F.M. Brennan), r.maini@ic.ac.uk (R.N. Maini), m.feldmann@ic.ac.uk (M. Feldmann). with the most common of them being rheumatoid arthri- tis (RA), multiple sclerosis (MS), systemic lupus ery- thematosus, insulin-dependent diabetes mellitus, Grave’s and Hashimoto’s thyroiditis, ankylosing spondylitis and Crohn’s disease. Although clinically distinct, all autoim- mune diseases have some similarities in their pathogenesis and involve the production of cytokines, important protein mediators that specifically regulate the inflammatory re- sponse, the tissue damage and the repair mechanisms [1]. In this article, we will review the role of cytokines in the pathogenesis of human autoimmune diseases, and discuss 1359-6101/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S1359-6101(02)00018-7