Inflammation

The cardinal signs — rubor (redness), calor (heat), tumor (swelling) and dolor (pain), described by Celsus, plus functio laesa (loss of function), added later — reflect underlying vascular events. Acute inflammation develops within minutes to hours and lasts days. After a brief arteriolar constriction, mediators such as histamine, nitric oxide and prostaglandins cause vasodilatation (redness and heat). Increased vascular permeability, chiefly through endothelial-cell contraction in post-capillary venules (histamine, bradykinin, leukotrienes) and through direct endothelial injury, lets protein-rich fluid (exudate) escape, causing swelling, concentrating red cells and slowing flow (stasis). Leukocytes then marginate, roll, adhere and transmigrate — neutrophils dominate the first 6–24 hours, followed by monocytes/macrophages at 24–48 hours — and phagocytose the offending agent. Pain results from bradykinin and prostaglandin E2 sensitising nociceptors, and from tissue tension.

Mediators come from cells (histamine and serotonin; prostaglandins via cyclo-oxygenase and leukotrienes via 5-lipoxygenase from arachidonic acid; platelet-activating factor; cytokines TNF-α, IL-1, IL-6 and chemokines; reactive oxygen species) and from plasma (complement C3a and C5a, kinins such as bradykinin, the clotting and fibrinolytic systems). Systemically, IL-1, IL-6 and TNF-α produce the acute-phase response: fever (cytokines act on the hypothalamus via the circumventricular organs to induce prostaglandin E2, raising the thermoregulatory set point), hepatic synthesis of acute-phase proteins (C-reactive protein, serum amyloid A, fibrinogen — which raises the ESR — ferritin, hepcidin, haptoglobin; albumin and transferrin fall), neutrophil leukocytosis with a left shift, tachycardia, anorexia and malaise.

Outcomes are resolution (mediator decay, neutrophil apoptosis and efferocytosis, pro-resolving lipoxins and resolvins, IL-10, TGF-β), healing by fibrosis (scar), abscess formation, or progression to chronic inflammation — a prolonged process (weeks to years) dominated by macrophages, lymphocytes and plasma cells, with simultaneous tissue destruction and attempted repair (angiogenesis, fibrosis), caused by persistent infection (TB, syphilis), autoimmunity or prolonged exposure to toxic agents (silica, oxidised lipids in atherosclerosis). Granulomatous inflammation is a distinctive form of chronic inflammation.