title: The utility of animal models in developing immunosuppressive agents.
abstract: The immune system comprises an integrated network of cellular interactions. Some responses are predictable, while others are more stochastic. While in vitro the outcome of stimulating a single type of cell may be stereotyped and reproducible, in vivo this is often not the case. This phenomenon often merits the use of animal models in predicting the impact of immunosuppressant drugs. A heavy burden of responsibility lies on the shoulders of the investigator when using animal models to study immunosuppressive agents. The principles of the three R׳s: refine (less suffering,), reduce (lower animal numbers) and replace (alternative in vitro assays) must be applied, as described elsewhere in this issue. Well designed animal model experiments have allowed us to develop all the immunosuppressive agents currently available for treating autoimmune disease and transplant recipients. In this review, we examine the common animal models used in developing immunosuppressive agents, focusing on drugs used in transplant surgery. Autoimmune diseases, such as multiple sclerosis, are covered elsewhere in this issue. We look at the utility and limitations of small and large animal models in measuring potency and toxicity of immunosuppressive therapies.
authors: Department Transplant Surgery, City Hospital, 11th floor, Lisburn Road, BT9 7AB Belfast, UK.
authors: James
authors: J
authors: McDaid
authors: School Pharmacy, Queen׳s University, Belfast, UK.
authors: Christopher J
authors: CJ
authors: Scott
authors: Centre for Infection and Immunity, Queen׳s University, Belfast, UK.
authors: Adrien
authors: A
authors: Kissenpfennig
authors: Laboratory of Experimental Surgery, Research Center, CHUM, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
authors: Huifang
authors: H
authors: Chen
authors: Department Surgery, Division of Transplantation, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
authors: Paulo N
authors: PN
authors: Martins
mesh_terms: D023401:Animal Use Alternatives; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use* / Q000633:toxicity; D009928:Organ Specificity; D013045:Species Specificity
chemical_list: D007166:Immunosuppressive Agents
keywords: Animal model; Drug; Immunology; Immunosuppression; Transplant