Thymogen

The immunomodulatory dipeptide L-Glu-L-Trp was isolated by reversed-phase HPLC from the calf-thymus peptide complex Thymalin and subsequently synthesized as the drug Thymogen. Both the natural complex and the synthetic dipeptide enhanced T-cell differentiation, improved T-cell recognition of peptide-MHC complexes, altered intracellular cyclic nucleotide levels, and increased cytokine secretion by blood lymphocytes; the synthetic dipeptides additionally augmented neutrophil chemotaxis and phagocytosis. Clinical use of Thymalin and Thymogen in patients with chronic pathology was reported to help prevent development of immune dysfunction.

This is the foundational paper describing how the Glu-Trp dipeptide (marketed as Thymogen) was pulled out of a natural calf-thymus extract and then made synthetically. In lab and clinical work the authors report it helps immune cells (especially T-cells) mature and work better and boosts the germ-eating activity of other white blood cells. It is authored by the drug's Russian developers, so it reflects the originators' findings rather than fully independent confirmation.

In a study of 76 female rats, lifelong administration of the immunomodulatory dipeptide L-Glu-L-Trp (Thymogen) reduced the aging rate (0.0041 vs 0.0071 day^-1 in controls) and extended maximum lifespan (1048 vs 949 days, P < 0.001). Total tumor incidence was 1.5-fold lower, malignant tumor incidence 1.7-fold lower, and hematopoietic malignancies 3.4-fold lower in treated animals versus controls, linking the peptide's immunomodulation to reduced spontaneous carcinogenesis.

Rats given the Glu-Trp dipeptide throughout life aged more slowly, lived longer, and developed fewer tumors than untreated rats, an effect the authors attribute to the peptide keeping the immune system more active. This is an animal study, not a human trial, and it again comes from the peptide's original Russian developers, so the results need independent replication before being applied to people.

Using the human THP-1 monocyte/macrophage cell line, this study evaluated several short thymic-derived peptides including Thymogen (Glu-Trp). All tested peptides reduced LPS-stimulated TNF-alpha and IL-6, and Thymogen was the most effective peptide at attenuating IL-17 release from activated macrophages. Thymogen also markedly reduced adhesion of treated monocytes to endothelial cells, indicating an anti-inflammatory modulation of monocyte/macrophage activity in vitro.

In this more recent lab study using human immune cells grown in a dish, the Glu-Trp peptide calmed inflammation, lowering several inflammatory signaling molecules and making immune cells stick less to blood-vessel lining cells. It is a cell-culture study (not a clinical trial), and while the research group is Italian, one of Thymogen's original Russian developers is a co-author.