The discovery and development of antiinflammatory drugs

✍ Scribed by Kay Brune; Burkhard Hinz

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 406 KB
• Volume: 50
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.20424

✦ Synopsis

Inflammation was one of the earliest recognized and defined disease entities. Celsus characterized inflammation by the 4 cardinal signs, namely, pain (dolor), redness (rubor), warmth (calor), and swelling (tumor); Galenius (others say Virchow) added "loss of function" (functio laesa). These signs are still valid. Attempts to modify these symptoms by drug therapy are at least as old as the cardinal signs themselves.

Dioscourides, a Greek physician of the Roman army, prescribed extracts of willow bark for joint pain, an approach that was later propagated by Hildegard von Bingen in continental Europe and, of course, by the Reverend Stone in his famous letter to the Royal Society of Medicine in London (1,2). The physicians of those times recognized that local inflammation often accompanies "general inflammation" manifested by fever and malaise. The reason for this association was only recently uncovered, namely, the release of the pyrogenic cytokines, such as tumor necrosis factor ␣ (TNF␣) and interleukin-1, that are produced by inflamed tissue and mediate generalized symptoms. Fever, along with malaise, was regarded by the Hippocratic School as a cardinal sign of an imbalance in the body fluids, resulting in disease (3). Based on this Hippocratic concept, purgation, sweating, and bloodletting were employed to alleviate inflammation and other diseases on the assumption that these procedures could change the composition of the body fluids. Such practices were continued until the 19th century and were used to cure all types of diseases, including mental disorders (4). Not surprisingly, these measures yielded limited success.

A more rational approach to treating inflamma-