Modification of prostaglandin generation by L-histidine--possible pathogenetic implication in rheumatoid arthritis.

The effect of l-histidine on arachidonic acid metabolism was studied in rabbit splenic fibroblast cultures and human platelets. The noradrenaline-stimulated generation of PGE2 in fibroblast cultures was inhibited by l-histidine dose dependently. In the same way l-histidine diminished the aggregation-induced synthesis of TXB2 in human platelets. In contrast to this, after incubation with l-histidine the generation of PGE2 in activated platelets increased in a dose dependent way up to 240% of pretreatment values. The further increase of l-histidine concentration resulted in an inhibition of platelet PGE2 synthesis. The present results demonstrate a differential influence of the amino acid l-histidine on cell arachidonic acid metabolism. It is concluded that the supposed anti-rheumatic property of l-histidine is caused by its effect on the synthesis of prostaglandins which are known to be mediators of inflammation.