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

Immunomodulatory molecule L-Glu-L-Trp was isolated from natural calf thymic peptide complex Thymalin by reverse-phase high performance liquid chromato graphy. On the basis of the synthesized dipeptide a pharmaceutical was desi gned containing this compound, which later receives the brand name Thymogen (R). The agent activated T-cell differentiation, T-cell recognition of pept ide-MHC complexes, induced changes in intracellular composition of cyclic n ucleotides, and activated neutrophilic chemotaxis and phagocytosis. The eff ect of dipeptide on survival, life span and spontaneous turner development was studied in female rats. Seventy-six, five-month-old outbred female rats were randomly subdivided into two groups and were subcutaneously injected with 0.2 mi of normal saline (controls, 32 rats) or with 5 mug/rat of the d ipeptide L-Glu-L-Trp, dissolved in 0.2 mi of saline (44 rats), 5 times per week for 12 months. Animals were monitored up to their natural death and al l the tumors discovered were studied microscopically. Mean life span of rat s in both groups was similar but that of 10% maximum survived control rats constituted 949 +/- 16.1 days, whereas in the dipeptide-treated rats this v alue was 1048 +/- 21.1 days (P < 0.001). Six out of 44 rats treated with th e drug survived over the maximum life span of control rats (965 days). The aging rate indicated as a in the Gompertz equation, was 0.0071 days(-1) in controls and 0.0041 days(-1) in rats exposed to L-Glu-L-Trp. Total tumor in cidence was 1.5 times lower (P < 0.01), malignant tumor incidence 1.7 times lower (P < 0.01), and hematopoietic malignancies (leukemias and lymphomas) 3.4 times lower (P < 0.02) in rats exposed to the dipeptide in comparison with controls. Thus, treatment with L-Glu-L-Trp delayed aging rate and decr eased spontaneous tumor incidence in rats.