Immunomodulatory synthetic dipeptide L-Glu-L-Trp slowsdown aging and inhibits spontaneous carcinogenesis in rats

Abstract

Immunomodulatory molecule L-Glu-L-Trp wasisolated from natural calf thymic peptide complexThymalin by reverse-phase high performance liquidchromatography. On the basis of the synthesizeddipeptide a pharmaceutical was designed containg this compound, which later receives the brand nameThymogen®. The agent activated T-celldifferentiation, T-cell recognition of peptide-MHCcomplexes, induced changes in intracellularcomposition of cyclic nucleotides, and activatedneutrophilic chemotaxis and phagocytosis. The effectof dipeptide on survival, life span and spontaneoustumor development was studied in female rats. Seventy-six, five-month-old outbred female rats were randomlysubdivided into two groups and were subcutaneouslyinjected with 0.2 ml of normal saline (controls, 32 rats) or with 5 µg/rat of the dipeptideL-Glu-L-Trp, dissolved in 0.2 ml of saline (44 rats),5 times per week for 12 months. Animals were monitoredup to their natural death and all the tumorsdiscovered were studied microscopically. Mean lifespan of rats in both groups was similar but that of10% maximum survived control rats constituted949 ± 16.1 days, whereas in the dipeptide-treatedrats this value was 1048 ± 21.1 days (P < 0.001).Six out of 44 rats treated with the drug survived overthe maximum life span of control rats (965 days). Theaging rate indicated as α in the Gompertz equation,was 0.0071 days⁻¹ in controls and 0.0041 days⁻¹ in rats exposed to L-Glu-L-Trp. Totaltumor incidence was 1.5 times lower (P < 0.01),malignant tumor incidence 1.7 times lower (P < 0.01),and hematopoietic malignancies (leukemias andlymphomas) 3.4 times lower (P < 0.02) in rats exposedto the dipeptide in comparison with controls. Thus,treatment with L-Glu-L-Trp delayed aging rate anddecreased spontaneous tumor incidence in rats.