Inflammation may be initiated by either en- dogenous or exogenous factors. It can be an acute response to trauma (as in a ligament tear) or a chronic response (as in autoim- mune diseases such as RA). Infection and crystalline deposits also can provoke an in- flammatory response that will persist until the underlying cause is eliminated.

When trauma is the cause, inflammation promotes healing. As wounds heal, metabol- ic activity consumes oxygen, resulting in a hypoxic environment that stimulates prolif- eration of fibroblasts and production of blood vessels (angiogenesis) at the site. Anoxia leads to increased levels of enzymes such as cathepsin, which provide a means to remove dead tissue and debris.6 The process is re- versed with angiogenesis and tissue reperfu- sion; thus begins the next stage of wound healing and a return to homeostasis.

Viral or bacterial infection is also a trig- ger for inflammation, as it promotes an im- mune response that recruits leukocytes to destroy the antigen. At the same time, this response increases cytokine production and vascular permeability. When the infection is controlled, the acute inflammation subsides. However, with chronic autoimmune disease, the infection may produce bacterial or viral compoundsthatalterT-cellrecognitionand the tissue response.

With diseases such as RA or systemic lu- pus erythematosus (SLE), the trigger may be a T-cell–mediated immune response to an autoantigen such as an epitope of type II collagen7 or a nucleoprotein, respectively.8,9 Because a specific antigen has not been identified as the initiator of either disease, both must be considered to be multifactorial processes of unknown etiology.

Crystal-induced arthritis, namely gout and pseudogout, is an acute process that may be treated with medication but may also de- velop into a chronic synovitis or recurrent acute inflammation. With gout, the trigger is deposition of the endogenously produced mi- crocrystalline compound monosodium urate within the joint. With pseudogout, the agent typically is calcium pyrophosphate dihy- drate. Hydroxyapatite and calcium oxalate can also initiate inflammation. These crystals form nodes or tophi that act as irritants, causing the adjacent tissue to become inflamed.