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 P-if 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 beta(1)-integrin system seems to provide a common pathway by which the cells can lower as well as raise P-if. 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 P-if limits the uptake of therapeutic agents.