Tuftsin: Our Natural Autoimmune Switch

Balance The Immune System With Tuftsin 

Tuftsin can powerfully balance and regulate the immune systemR




  1. Basics
  2. Mechanism Of Action
  3. Benefits
  4. How To Get/Increase Tuftsin
  5. My Experience
  6. Caveats
  7. More Research


Tuftsin is naturally produced in the spleen. R

It was found by scientists Najjar and Nishioka in 1970 and named after Tufts University. R R

It can play an important role in:

  • Splenectomy (Spleen Removal) R
  • Infections R
  • Boosting the immune system R
  • Celiac disease R
  • Hypersplenism R
  • Systemic lupus erythematosus (SLE) R R
  • Sickle Cell Disease R
  • Dermatitis herpetiformis R
  • Rheumatoid arthritis R
  • Kidney disease
  • Thrombocytopenia R
  • Ulcerative colitis R
  • Vasculitis R
  • Multiple Sclerosis R
  • General Anxiety Disorder R
  • Depression R
  • Black Fever R
  • HIV/AIDS (deficiency) R
  • Cirrhosis (impaired activity) R

Mechanism Of Action




Tuftsin shifts the immune response from an inflammatory response to an anti-inflammatory responseR

It does this by shifting T helper cells from Th1/TH17 turn into Th2/Treg (ie TNF-a -> IL-4, IL-10, TGFb1). R

Tuftsin (like ghrelin) can shift microglia into a M2 microglial anti-inflammatory response (as seen above). R R

Tuftsin signals through Nrp1 and TGFB pathways.  R

Tuftsin competes with VEGF for binding to Nrp1. R R

Tuftsin regulates cyclic nucleotides and Cat+ concentration in the cell. R

Selank, a synthetic analogue of tuftsin, influences the concentration of monoamine neurotransmitters and induce metabolism of serotonin. R R R

Selank can decrease the expression of IL-6 and balance T helper cells’s production of cytokines. R

Selank affects the activity of carboxypeptidase H and phenylmethylsulfonylfluoride-inhibited carboxypeptidase in rat nervous system tissue. R

Selank effects the XCL1–XCR1 axis, Il2rg gene expression and C3 gene expression. R


1. Turns Off Autoimmunity



Autoimmune disorders happen when the immune response is overactive and will not turn off. R

People who have their spleen removed have a higher chance of getting an autoimmune disorder. R

Tuftsin is able to shift the Th1 autoimmune response to a Th2 response, and thus turn off an autoimmune response. R

2. Ameliorates Multiple Sclerosis and Regenerates Myelin



Multiple sclerosis (MS) is an autoimmune disease in which T cells, microglia and macrophages attack the myelin sheath that protects the nerve fibers in the brain and spinal cord. R

During multiple sclerosis, T cells become activated in the central nervous system (CNS) and attack the blood brain barrier (BBB). R

It generates an inflammatory cascade of cytokines and chemokines that cause demyelination of the CNS. R

Tuftsin activates microglia to promote a M2 anti-inflammatory response, allowing the regeneration of myelin. R R

Tuftsin is even more powerful in MS when combined with glutamate to generate neuronal-conditioned medium. R

3. Helps With Anxiety and Stress



Selank is commonly sold over the counter in Russia.

Selank, has shown in clinical trials to be useful against general anxiety disorder (GAD). R

Unlike benzodiazepines, it is not sedating and does not cause addiction or withdrawal. R

Although it can enhance the effects of benzodiazepines. R

It is anxiolytic like other opioids. R

On possible mechanism for selank’s effect on anxiety is it’s effects on the GABAergic system. R

In rats, tuftsin was able to reduce anxiety-phobic states significantly (by normalizing serotonin levels), without effecting weight. R R

4. Has Anti-Depressant Properties

In rats, selank in high doses (1000-2000 microg/kg), was able to counteract symptoms of depression. R

Selank was able to stimulate hibernating squirrels and induced a more exploratory-like behavior. R

5. Is Neuroprotective, Protecting Against Stroke and Epilepsy



Tuftsin can activate a M2 anti-inflammatory microglial response, increasing specific genes that help with neuroprotection. R

Selank has been shown to rapidly elevate brain derived neurotrophic factor (BDNF) in the hippocampus when taken intranasally (in rats). R

Also, selank can regulate ion homeostasis of the hippocampus (in rats). R

Tuftsin is also able to prevent damage from reactive oxygen species in the brain, helping protect against dopaminergic neuronal cell loss. This can possibly help Parkinson’s disease. R

Tuftsin works on MAO-A, MAO-B, and acetylcholinesterase and activates dopamine metabolism. R

Activated microglia/macrophages are important contributors to brain injury after hemorrhagic strokesR

If used soon after the onset of hemorrhage, tuftsin may improve injury volume, edema, and degenerating neurons, while improving the neurological functional outcome. R

In animals, tuftsin is able to protect against epileptic damage caused by high doses of penicillin. R

6. Is Anti-Microbial, Anti-Fungal, and Anti-Viral



Tuftsin deficiency, either hereditary or following splenectomy, can result in an increased susceptibility to certain infections (H. influenza, pneumococci, meningococci and salmonella). R

Tuftsin initiates the production by phagocytes of superoxide and nitroxide radicals, which are necessary for killing phagocytized bacteria. R

Tuftsin can thoroughly destroy several microbes and viruses (not exclusive list):

  • Influenza A R
  • Mycobacterium tuberculosis R
  • Herpes Simplex Virus (HSV1 and HSV2) R
  • Cytomegalovirus (CMV) R
  • Encephalomyocarditis virus (EMCV) 
  • Pneumococcus R
  • Micrococcus glutamicus R
  • Gastroenteritis coronavirus (with muramyl dipeptide and L. casei) R R
  • Staphylococcus aureus R
  • Bacillus Subtilis and cereus R
  • Sarcina flava R
  • Streptococcus faecalis R
  • Gaffkya tetragena R
  • Diplococcus pneumonia R
  • Glavobacterium flavescens R
  • Pasteurella pseudotuberculosisR
  • Listeria R
  • Candida albicans R R
  • Cryptococcus neoformans (even more effective combining with nystatin) R

7. May Help Against Cancer 



Tuftsin stimulates macrophages from the liver spleen and lymph nodes and can mobilize other while blood cells to fight against cancer. R

In vitro, tuftsin can inhibit the growth of tumor cells. R

Tuftsin had anti-tumor properties in both mice and beagles, without causing toxicity to the animals. R R

In animal models, tuftsin has been shown to help:

  • Sarcoma and fibrosarcoma R R
  • Leukemia R

Tuftsin-based, enediyne-energized, and EGFR-targeting fusion proteins exert highly antitumor efficacy with CD47 modulation (esp in EGFR- and CD47-overexpressing cancers). R 

8. Helps Sepsis Recovery and Outcome

Sepsis is still the leading cause of death among critically ill patients in intensive care units. R

Survivors usually suffer from an impaired quality of life. R

There is a significant loss of immunocytes, including B/T lymphocytes, dendritic cells (DCs), gastrointestinal epithelial cells, even thymocytes from the beginning of sepsis as shown both in animal models and septic patients. R

In mice, a tuftsin-derived T-peptide was able to prevent immunosuppression and improve the survival rate. R

9. Helps with Lupus and Arthritis



Tuftsin combined with phosphorylcholine (called TPC) was able to hamper lupus development in mice (by enhancing TGFB and IL-10, while inhibiting IFN-gamma and IL-17). R

TPC was also able to reduce proinflammatory cytokines and increased anti-inflammatory cytokine expression in early rheumatoid arthritis onset. R

10. Helps with Inflammatory Bowel Disease Pain

Inflammatory bowel disease (IBD) is comprised of two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC). R

In mice, TPC was able to significantly prevent colitis symptoms (TNFa, IL-17 and IL-1b was supressed while IL-10 expression was increased). R 

11. Increases Efficacy of Vaccines



A vaccine conjugating tuftsin to infectious hepatitis vaccines (HE-ORF2 and HA-VP1), made it more effective. R

Also, conjugating tuftsin to four copies of M2e of influenza A enhanced the antigen-specific immune response. R

Linking tuftsin to envelope glycoproteins 41 (gp41) and 120 (gp120) of HIV enhanced the antigen-specific immune responses. R

Enhanced responses to the combined protein vaccine have been shown to be more effective intranasally, rather than intramuscular. R

Oligotuftsin derivatives can be considered as promising carriers for synthetic vaccines. R



How To Get/Increase Tuftsin



Here are ways (places) to get or increase tuftsin naturally:


  • TBR1 antagonists
  • EG00229 (Neuropilin-1 inhibitor) 

My Experience

I have tried Selank intranasally for prolonged periods (along with N-Acetyl-Selank and N-Acetyl-Selank Amidate).

 I have noticed decreased anxiety and an extreme calmness, almost like a oneness. 

I am able to focus better and not get as easily distracted (as almost like Theanine on ‘roids). 

I also noticed that my conversations became easier with others.

One experiment I tried was eating inflammatory foods that I knew would hurt my stomach. As a result, I seemed to get less of an inflammatory response.


In other’s experience, Selank has been reported to synergize well with semax, although I never really had felt any synergistic effects. R


Tuftsin can decrease hypothalamic TRH and increase TSH levels, in a dose-related manner. R

One study reported that tuftsin was not immunogenic itself, but it could strengthen the humoral immune response to the antigen to which it was linked. R

Selank, like all lipophilized peptides, needs refrigeration to remain stable within sterile water solutions, such as bacteriostatic water concentrations. R

Tuftsin has low toxicity (safe up to a dose of 0.96 mg/kg body weight). R

Extensive augmentation of white blood counts and enhanced cytotoxicity of lymphocytes are notable at levels of 0.04 to 0.96 mg peptide per kg. R

As the normal tuftsin serum level is 250–500 ng/ml and the LD50 dose of tuftsin is 2.4 mg/ml, a serum level of 60 µg/ml is a suitable physiological concentration for applying tuftsin in therapeutic studies. R

Coinjection of carrageenan, a macrophage inhibitor, with tuftsin resulted in complete neutralizing of the activity of the peptide. R

HL60 cells can be stimulated by tuftsin to secrete TNF. R

Tuftsin deficiency is manifested by severe recurrent infections involving primarily the skin, lymph nodes and lungs. R

More Research

  • C-Reactive Protein (CRP) contains three tuftsin-related sequences: Lys-Pro-Arg, Thr-Lys-Pro, and Thr-Lys-Arg. R