増殖型炎症の薬物制御
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概要
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Regulation of chronic proliferative inflammation by drugs was reviewed with special reference to collagen metabolism which is an important inflammatory reaction in the proliferative phase of inflammation. An animal inflammation model, called"the carrageenin-air-pouch inflammation in rats, "is an excellent model for the chronic proliferative inflammation. Collagen in the granulation tissue induced by carrageenin is mainly types I and III collagens. The half-life of collagen is about 3.5 d in granulation tissue, indicating that the collagen breakdown in the proliferative inflamed tissue is very rapid compared with that in normal tissues, in which the half-life of collagen is about 60-70 d. This rapid breakdown of collagen may occur both extra-and intra-cellularly by proteinases such as collagenase, gelatinase and cathepsin B. On the basis of the results of experiments using proteinase inhibitors, it is suggested that a neutral proteinase (s) which activates a latent collagenase plays an important role in the rapid breakdown of collagen in granulation tissue. Anti-inflammatory steroids suppress and β-aminopropionitrile enhances the collagen breakdown in granulation tissue, though the mechanism is unclear at the present time. Inhibitory effect of anti-inflammatory steroids on collagen synthesis is significantly greater than that on the synthesis of noncollagen protein in granulation tissue. This greater inhibition of collagen synthesis by the steroids is due to a strong inhibition of procollagen synthesis without affecting the hydroxylation of procollagen, the precursor of collagen. On the other hand, D-penicillamine inhibits the hydroxylation of procollagen by chelating ferrous iron, a cofactor of prolyl hydroxylase, resulting in the selective inhibition of collagen synthesis. In addition, a strong inhibition of collagen synthesis by the steroids is discussed in connection with the steroid-induced inhibition of the deoxyribonucleic acid synthesis in granulation tissue. Two modes of drug action for the enhanced resorption of the pre-formed granulation tissue can be considered ; one is"suppression type"of drugs such as anti-inflammatory steroids which inhibit collagen breakdown and the syntheses of collagen and noncollagen protein, and the other is"enhancement type"of drugs such as CaEDTA and progesterone which increase the degradation of noncollagen protein only.
- 社団法人日本薬学会の論文
- 1982-03-25