In their short leader for the British Journal of Sports Medicine, A. Scott et alia ask a question  that has puzzled me throughout my graduate career. I have yet to come across a satisfactory definition of inflammation, the answer sooner or later coming to rest at a point of tautology; there exists a hundred and zero definitions for inflammation. It is redness, pain and swelling, except when it isn’t, and functions via immune cells such as leukocytes, except when it doesn’t, secreting inflammatory molecules such as cytokines and prostaglandins. Are the cytokines and prostaglandins the inflammation, or a signal for cells to initiate inflammation, or both? What precisely do cytokines do, other than increase the production and secretion of more cytokines?
Looking at the history of the word, it was coined by Celsus in 1 A.D. and centered on the clinical symptoms now referred to as “classical inflammation,” those being rubor et tumor cum calore et dolore (redness and swelling with heat and pain). Rudolf Ludwig Carl Virchow, a few years after coming perilous close to a Trichinella-inoculated sausage duel with Otto von Bismarck (look it up), added functio laesa (loss of function) to the classical inflammation canon. Virchow’s cellular pathology view of inflammation supplanted the humoral one of Galen of Pergamon, which had been dominant from the 3rd to 19th centuries. Other than the general differences in philosophy between humoralism and medicine, Virchow specifically believed inflammation to be inherently pathological, whereas Galen maintained it was a beneficial response. As microscopy allowed for cellular visualization, the cellular theory of inflammation, in which leukocytes move to and proliferate in an injured area from their origin in the vessels, swept the field. This was not to last long, historically speaking, as molecular biology allowed the measurement of, and shifted the focus towards, cellular protein production. Most cells, many more than the immune cells identified in inflamed tissues by microscopy, are capable of producing and responding to the cytokines, chemokines, eicosanoids etc. associated with inflammation. A new term, metabolic inflammation, has been coined to describe the presence of higher than normal levels of these molecules in cells, tissues or blood that are not simultaneously exhibiting classical inflammation. Thus is the history of inflammation; the authors then comment on the use of anti-inflammatory drugs in sports medicine and how a better understanding of the “complex cascade that is inflammation” is desirable.
One thing that occurs to me about inflammation is that it must either unify disparate events (infection, tissue trauma, oxidative stress), or be broken up into subsets of according to differences of cause and effect. For example, it’s hard to imagine that activation of toll-like receptor 4 (Tlr4) or nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) would occur in the same way different insults, or that cells and tissues would want to respond in that same way to them. The main question, as I see it, is whether inflammation is a very general and conserved cell response to damage, or a more specific reaction to defined antagonists.
Consider an airplane in the sky as an analogy for the cell. Grant to the plane, like the cell, the ability to produce its interior contents (seats, passengers, food carts etc.). Imagine then that the airplane receives damage resulting in a hole in its side. Depending on the extent of damage, the plane may start to leak its contents. Passengers, broken seats and the like will fall out of the plane. Since we have given this plane the cellular ability to produce its contents, it will make more carts and flight attendants, some destined to exit by the same hole, in an attempt to maintain homeostasis. From a certain perspective, and with certain measurement tools, it may appear that the production and secretion of people and objects from the plane is causing the damage. One of the seats may fall and smash into another plane, causing damage to it and thus proliferating the production and secretion of intra-plane contents. If whatever originally damaged the plane is more difficult to measure or conceptualize than the secreted contents, it will be difficult to maintain the position that the damage is causing the secretion and not vice versa.
This analogy illustrates one of the dangers, often completely ignored, of molecular biology: artefact. If you find something at higher concentrations associated with injury, how do you go about ascribing causation? In molecular biology, when ones “looks” for something, they often find it. The bar for proving a molecular mechanism should be set quite high. What is being measured should be clearly stated and not over-stated. When a molecule is proposed to be associated with inflammation, and it’s presence at high levels is measured to indicate inflammation, it is an inappropriate leap to then define the presence of high levels of that molecule as inflammation. That is the essence of the hundred and zero definitions for inflammation; a hundred ad hoc definitions, zero explanatory ones.
 Scott a. What is “inflammation”? Are we ready to move beyond Celsus? Br J Sports Med 2004;38:248–9.