Tuftsin

Immune & Anti-Inflammatory

Also known as: Thr-Lys-Pro-Arg, TKPR, Tuftsin Tetrapeptide

Endogenous ImmunostimulantsResearch phase: Extensive preclinical, limited clinical dataRegulatory: Not approved as a standalone pharmaceutical in any jurisdiction. Extensively studied since its discovery by Najjar in 1970. Research peptide. Its derivative Selank is approved in Russia.

Mechanism

Tuftsin is a naturally occurring four-amino-acid peptide that your body produces from IgG antibodies when they pass through the spleen. It is one of the body's primary signals for activating macrophages and other immune cells to eat and destroy pathogens (phagocytosis). People without a functioning spleen are tuftsin-deficient and more susceptible to infections. It is also the molecular ancestor of Selank — Russian scientists extended tuftsin's sequence to create Selank, one of the most popular anxiolytic peptides.

Technical detail

Tuftsin (Thr-Lys-Pro-Arg) is an endogenous tetrapeptide cleaved from the CH2 domain of the IgG heavy chain (residues 289-292) by two sequential enzymatic steps: splenic tuftsin endocarboxypeptidase removes the C-terminal Fc region, then leukokinin (a membrane-bound enzyme on neutrophils/macrophages) liberates the active tetrapeptide. Binds to specific tuftsin receptors (neuropilin-1/NRP1) on monocytes, macrophages, neutrophils, and NK cells. Activates phagocytosis, chemotaxis, and respiratory burst (superoxide production) via Fc receptor-independent mechanisms. Enhances antigen presentation by upregulating MHC class II expression. Stimulates NO production in macrophages. Modulates T-cell immunity by promoting Th1 responses. Deficiency associated with splenectomy, sickle cell disease, and certain immunodeficiencies — correlating with increased infection susceptibility. Basis for Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which extends tuftsin with a Pro-Gly-Pro stabilizing sequence.