THE TORTUOUS MAZE OF INFLAMMATION - FROM HIEROGLYPHIC FLAMES TO GASEOUS FREE RADICALS

Inflammation is the reaction of living tissues to injury. The earliest record of a word which can be translated as inflammation appears in an Egyptian papyrus of the second millenium B.C. The hieroglyphs are reported to contain a determinitire which represents a flaming brazier conveying the idea of heat in connection with wounds (Majno, 1975). Hippocrates (460-380 B.C.) knew inflammation as phlegmone ("the burning") but it was the Roman writer Cornelius Celsus who, in describing how flesh reacts to infection, listed the principal symptoms of inflammation known tO all veterinary undergraduates as redness, swelling, heat and pain; to which, in the last century, Rudolph Virchow added loss of function (Ryan & Majno, 1977). These signs represent the clinical manifestation of successive complex vascular and immunological reactions which aim to minimize the effect on the body of an insult and lead to repair and restoration of normal function. It was a pupil of Virchow, Julius Cohnheim (1839-1884) who noticed that as tissues were irritated there were changes in blood vessels, blood flow and cellular activity which might explain the "cardinal signs" of inflammation proposed by Celsus (Cohnheim, 1889). At about the same time, a Russian worker, Elie Metchnikoff (1845-1916) showed that phagocytosis by white blood cells was a defence mechanism against invading micro-organisms and suggested that the purpose of inflammation was to bring phagocytes to a site of injury (Metchnikoff, 1893). Soon afterwards, early immunologists realized that an increase in vascular permeability of blood vessels in the inflamed area would also allow a rapid accumulation of antibodies in infected tissues to assist local defence. As Florey (1962) has declared, inflammation is a process not a state. In their review in this issue of the Journal, Dr Fiona Cunningham and Professor Peter Lees illustrate how the pathophysiological changes underlying the inflammatory process are brought about by chemical mediators acting locally within the tissues. The authors have summarized much of the present knowledge about these mediators and how they act on tissues, circulating cells and the microcirculation as well as interacting with each other. It is necessary to know why inflammatory cells accumulate and how they damage cells so as to understand the pathogenesis of disease and in order to develop rational treatments. There have been many developments in anti-inflammatory therapy in recent years as knowledge of some mediators and their control has expanded. In the veterinary species, work on the mode of action of aspirin-like drugs and the inhibition of the arachidonic acid metabolic pathways (Higgins, 1985; Lees & Higgins, 1985) has been followed by