New and active role of the interstitium in control of interstitial fluid pressure: potential therapeutic consequences

Here we present recent data indicating that the present view of the interstitium as a passive fluid reservoir has to be revised. The connective tissue cells and extracellular matrix have a role in the control of Pif and a fundamental role in the rapid development of edema in burns and in the initial swelling in inflammation by generating a lowering of interstitial fluid pressure. In this process, the β1‐integrin system seems to provide a common pathway by which the cells can lower as well as raise Pif. Inflammatory swelling can be reversed by endo‐ and exogenous substances, thereby suggesting that the connective tissue can serve as a novel target for pharmacological intervention. Furthermore, the new knowledge in interstitial physiology on means to reduce interstitial fluid pressure may be of importance for drug delivery into solid tumors, where a high Pif limits the uptake of therapeutic agents.