VOLUME 1 - ISSUE 3 - INFLAMMATION RESEARCH LIFETIME ACHIEVEMENT AWARD FOR PROFESSOR DEREK WILLOUGHBY

The first Inflammation Lifetime Achievement Award was recently presented by the International Inflammation Research Association (IAIS) to Professor Derek Willoughby. This award recognises those who have made major and extensive contributions to the field of inflammation research over their career. Derek Willoughby received his PhD from Cambridge University and was appointed lecturer in the Pathology/Immunology Department at St. Bartholomew's Medical College, London in the early 1960s, becoming Professor of Experimental Pathology in 1969. He is currently Emeritus Professor and Director of Experimental Pathology at the William Harvey Research Institute. Derek has received numerous distinctions and awards, including the Laureate de l'Academie de Medicine France and the Prix Jansen (1969), and was awarded the Chevalier dans l'Ordre du Merite by President Giscard d'Estaing for services to Anglo-French collaboration in medical research.

His early work on inflammation demonstrated, using novel models of immune and non-immune inflammation, the sequential release of pharmacologically active mediators: histamine, 5-HT, kinins and prostaglandins. The significance of adenylate and guanylate cyclase was examined in a variety of pleural models of inflammation, and the roles of these enzymes in the mode of action of anti-inflammatory drugs established. Derek has always fostered a close collaboration with clinical rheumatologists, which led to the description of both apatite deposition disease and mixed crystal deposition disease in osteoarthritis. These findings were then applied to relevant animal models using the crystals as an irritant in the pleural cavity.

During studies on cell-mediated immunity (CMI) Derek described one of the first cytokines - Lymph Node Permeability Factor (LNPF). This was capable of reproducing many features of classical CMI reactions and was involved in contact hypersensitivity, thyroiditis, experimental allergic encephalomyelitis, tuberculin reactions, and graft rejection. Anti-LNPF suppressed or markedly reduced pathology in many of these models. Subsequently, it was found in human tissue and related to the intensity of inflammation. The consequences of inflammation, namely tissue destruction, have been a main area of Derek's interest. Air pouch models were used extensively to examine the effects of different types of inflammation on cartilage breakdown. The loss of proteoglycan from cartilage was found to be directly related to granuloma development, itself related to angiogenesis, as well as macrophage derived gelatinase and elastase in its activation. Meanwhile, the methodology developed for this work was used to discover the erosive nature of subsets of osteoarthritic synovial fluids, finding free radical inactivation of ±2-macro-globulin to lead to excessive neutrophil elastase activity. Drug inhibition of angiogenesis significantly suppressed chronically-inflamed tissue and its erosive nature. This led to an examination of the role of angiogenesis in experimental models of tumours, dissecting the role of COX-1 and COX-2 in colorectal tumour angiogenesis, proliferation, and apoptosis, which established that the macrophage plays a central role and that dual inhibition of COX may provide the best growth inhibition in this type of carcinoma.

The role of hemeoxygenase-1 (HO-1), previously unrelated to inflammation, has also been explored by Derek's group, who showed that HO-1 is elevated during, and is responsible for, inflammation resolution. This work has been applied to human chondrocytes to afford protection against blood-induced cell death, for application to autologous transplants. Against the dogma of the period, COX-2 expression was found to be instrumental in inflammation resolution. As a result, the role of cyclopentenone prostaglandins, NFkB and apoptosis in polymorphs and macro-phages during resolution is a new and developing field currently under investigation.

Derek's most recent work has focused on those factors involved in the resolution of the inflammatory process (and seeking new therapeutic targets from the naturally occurring resolution factors). These range from apoptosis to signal transduction mechanisms, in particular the role of NFkB using molecular methods and genetically modified mice, in collaboration with Prof Michael Karin (San Diego USA). Improved methods of topical drug delivery are also being investigated. Many of the models developed for these studies have become industry standards for drug discovery and development. Derek has always had a passion and enthusiasm for this work and has encouraged open dialogue between scientists around the world. In the early 1970's, he began, in collaboration with others, a series of meetings on "Future Trends in Inflammation Research". It was these successes that prompted the initiation of the IAIS meetings in the early 1980's. These encouraged the formation of other inflammation societies and the constitution of the IAIS.

Derek's contributions have been immense and he has published approximately 600 articles over his 45 year career. We would like to congratulate him on an outstanding career in inflammation research and look forward to his continued contributions to this exciting field of science.

The above is an edited version of an article by Dr Alan Lewis, San Diego, California, on behalf of the IAIS Steering Committee).