Cell phenotype as a target of drug therapy in chronic inflammatory diseases

Many diseases share common pathological changes which could in principle be targets for new drugs. Vascular leakage of plasma and migration of cells i nto perivascular tissues are common to chronic inflammatory diseases such a s asthma, atherosclerosis, arthritis, and proliferative nephropathy as well as some non-inflammatory proliferative disorders such as diabetes mellitis . Individual components of plasma have been shown to stimulate cellular pro liferation, matrix deposition and phenotypic change, leading to tissue-dama ging structural changes. Whereas most anti-inflammatory drugs either downre gulate expression of inflammatory mediators or inhibit their actions on cel ls, there are alternate potential therapeutic strategies described here bas ed on moderating vascular leakage or its consequences in chronic diseases. The hypothesis is that drugs that can modify a cell's phenotype could be us ed to limit structural changes which accompany inflammation and thus reduce permanent debility resulting from these diseases. Such drugs include the d ifferentiating agents being developed for cancer therapy. (C) 2000 Harcourt Publishers Ltd.