Pathophysiology of tissue fluid accumulation in inflammation.

The potential role of extravascular factors for the local as well as systemic response to an inflammatory stimulus is addressed here in light of recent data from the trachea, serving as a surrogate for lower airways, and spleen, because of its role in the immune response and fluid volume regulation. From analysis of interstitial fluid from trachea it is apparent that the colloid osmotic pressure is high relative to plasma, suggesting a significant buffering capacity against oedema formation, and also that there is a significant local production of proinflammatory mediators to a systemic inflammatory stimulus. Inflammatory stimuli may furthermore result in a rapid reduction in interstitial fluid pressure, thus leading to increased filtration and oedema formation. Knowledge regarding the fluid phase within the spleen microenvironment can be gathered via analysis of drained lymph. During a septic response induced by lipopolysaccharide injection, the spleen contributes significantly to the production of pro- and anti-inflammatory cytokines, and may induce protracted inflammation because of a dominant role in IL-6 production. Significant amounts of immune cells exit via lymph, and acquire specific activation signatures having been exposed to the spleen microenvironment. Although often overlooked, extravascular or interstitial factors may therefore contribute significantly to the inflammatory process and thus the ensuing oedema associated with inflammation.