Review Cyclooxygenases and prostaglandins: shaping up the immune response Bianca Rocca a , Garret A. FitzGerald b, * a Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy b Department of Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA Received 7 August 2001; accepted 14 November 2001 Abstract The relevance of cyclooxygenases (COX) À 1 and À 2 and their products to inflammation, thrombosis and gastroprotection are well known. Their importance in the immune response was first recognized more than 25 years ago, but has only gained widespread attention recently. In this review, we attempt to integrate information on prostanoids and both the innate and acquired immune responses, including effects on leukocytes, antigen presenting cells, dendritic cells, T and B lymphocytes. Prostanoids may be relevant to immunotolerance, autoimmune disorders, transplantation, immunologic defense against tumors, acquired immunodeficiencies and viral infections. Insight into the role of prostanoids in immune function may afford novel therapeutic opportunities. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Lipid mediators; Prostaglandins; Cyclooxygenases; Immune response; Lymphocytes; Antigen presenting cells 1567-5769/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII:S1567-5769(01)00204-1 Abbreviations: AA, arachidonic acid; PL, phospholipases; PG, prostaglandins; Tx, thromboxane; HETE, hydroxyeicosatetraenoic acids; PPAR, peroxisome proliferator-activated receptors; LO, lipoxygenase; LT, leukotrienes; COX, cyclooxygenase; IL, interleukin; LPS, lipopolysaccaride; TNF, tumor necrosis factor; PGES, PGE 2 synthase; ASA, aspirin; NSAID, nonsteroidal anti-inflammatory drugs; GI, gastrointestinal; APC, antigen-presenting cells; AP, activator protein; Th, T helper cells; IFN, interferon; PMN, polymorphonuclear leukocytes; Mono, monocytes; MFG, macrophages; NK, natural killer cells; GM-CSF, granulocytic macrophagic-colony stimulating factor; fMLP, N- formyl-methyonil-leucil-phenylalanine; DC, dendritic cells; MHC, major histocompatibility complex; MDC, macrophage-derived chemokines; LAK, lymphokine-activated killer; DN, double-negative thymocytes; DP, double-positive thymocytes; SP, single-positive thymocytes; TCR, T cell receptor; FTOC, fetal thymic organ culture; RAG, recombinase activating gene; WT, wild type; EGF, epidermal growth factor; PBMC, peripheral blood mononuclear cells; NFAT, nuclear factor of activated T cells; CsA, cyclosporin A; EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; NOD, non-obese diabetic; EAU, experimental autoimmune uveitis; AD, atopic dermatitis; BLV, bovine leukemia virus. * Corresponding author. Tel.: +1-215-898-1184; fax: +1-215-573-9135. E-mail address: garret@spirit.gcrc.upenn.edu (G.A. FitzGerald). www.elsevier.com/locate/intimp International Immunopharmacology 2 (2002) 603 – 630