BIOCHEMISTRY OF INFLAMMATION By BEr•Ar•D IDSON, P..D.* Presented September 19, 1962, Seminar, New t•ork City INrI, AMMATION ranks next to pain as the greatest symptom of body difficulty or pathology. Menkin (1) defines inflammation as the "complex vascular, lymphatic and local tissue reaction elicited in higher animals by the presence of viable or of nonviable irritants." More simply, it is the local response of small blood vessels to injury. Inflammation is char- acterized to the naked eye by swelling, increased heat, redness, pain and disturbance of function. The swelling is due to the edema and congestion in the area. The inflamed area feels hot in comparison with the surround- ing areas because the dilated vessels bring a large amount of warm blood to the area. The redness results from the dilatation and congestion of the arterioles and capillaries. Pain is due to the swelling and tension on tissues with pressure on sensory nerves. The disturbance of body function is linked to the pain and destruction of the affected cells and tissue. Inflammation is not a static single event but a sequence of constantly changing interdependent reactions, each triggered by a previous alteration, a dynamic process by means of which cells and exudate infiltrate, ac- cumulate and finally destroy the integrity of connective tissue. Intimately and inseparably related to the inflammation is the repair process, whereby the tissues are protected from further injury. The agents causing the injury and hence leading to inflammation, may be of bacteriologic, physical, chemical or traumatic nature. Following a local acute injury there is disturbance in the flow through small blood vessels. A momentary con- striction of the capillaries is rapidly replaced by dilatation with an increase in blood flow. This dilation is also transitory and the blood flow slows down to almost stagnation. These local changes result chiefly in an in- crease in the permeability of the capillaries to the plasma proteins. Fluid plasma and white blood cells escape through the capillary walls into the surrounding tissues. This accumulation of fluid and cells is called an "exudate." Exudation is the primary and pivotal response on which all subsequent inflammatory responses depend (2). The fluid, or serous part of the exudate is, as noted, largely plasma and, when abundant, may be re- ferred to as inflammatory edema. * Dome Chemicals, Inc., New York 23, N.Y.

64 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The fluid plasma in the accumulated exudate coagulates in the area of injury with the precipitation of an abundant network of fibrin. This "walls off" the inflamed area, localizing the injurious agent and shielding adjacent tissues. The early fixation of, e.g., a bacterial irritant, allows time in which leukocytes can assemble to attempt to destroy the invader by phagocytosis. The first white cells to migrate through the vessel walls are the polymorphonuclear leukocytes, aided in some cases by a chemical stimulus, a process referred to as chemotaxis. Bacteria and products of injured tissue act as chemotactic agents, intensifying the emigration of the leukocytes from the blood vessels and directing them toward the injurious agent, leading them to actual contact with the foreign particle which makes phagocytosis possible. Acidosis develops in the area of inflammation (3), injuring the cells. These local changes in the hydrogen ion concentration of the exudate ap- pear to govern the cellular sequence in inflammation, consisting of poly- morphonuclear leukocytes followed by mononuclear phagocytes (4-6). When the pH falls below 6, all types of white cells are injured, and pus re- suits. Pus formation in acute inflammation is virtually a function of the hydrogen ion concentration (7). The mechanism of acidosis appears primarily referrable to a developing glycolysis (1), with the cellular sequence at the site of inflammation conditioned by the local pH, which in turn is determined by disturbance in the intermediary carbohydrate metabolism (7). CONNECTIVE TISSUE Inflammation can be considered to begin as a change in small blood vessels, or rather, as a change in the state of connective tissue components which determine the physiological properties of the small blood vessels. Whatever the organ affected, it is alteration in the connective tissue of the blood vessels which is fundamental to the development of inflammation. Connective and skeletal tissues are concerned throughout the body with the formation and maintenance of structure. They have as a common origin the embryonic mesenchymal cell, which in the course of differentiation forms the connective tissue proper, cartilage and bone (8). The texture of these tissues depends upon the orientation of the cells, their physical and chemical properties, the spatial organization of the various constituents with respect to each other and the relative amount of each substance pres- ent. The connective tissue cells are required to produce a wide variety of extracellular materials which determine to a large extent the processes of growth, regeneration and repair. The chief connective tissue cells are the fibroblasts and mast cells. The mast cells synthesize and release several substances that are important in the metabolism of connective tissue (9). Fluctuations in the rate of forma-