Thymulin
Also known as: Facteur Thymique Sérique, FTS, Serum Thymic Factor
Evidence: Preclinical
Overview
Zinc-bound nonapeptide hormone secreted by thymic epithelial cells; drives T-cell differentiation and shows immunomodulatory and anti-inflammatory effects in animal studies.
Thymulin is a zinc-dependent nonapeptide secreted by thymic epithelial cells, purified from pig serum in 1977 as facteur thymique serique (Dardenne et al., 1977). Zinc binding is what makes it active (Dardenne et al., 1982). Circulating levels peak in childhood and decline from adolescence onward (Consolini et al., 2000). Rodent work reports anti-inflammatory and antinociceptive effects in the central nervous system (Safieh-Garabedian et al., 2003), and a 2026 mouse study found it restrains age-associated myeloid inflammation and improves response to anti-PD-L1 therapy (Kanemaru et al., 2026). Human dosing data amount to one 1982 case series of three immunodeficient children given intravenous synthetic FTS (Bordigoni et al., 1982). No trial and no pharmacokinetic study exists.
Benefits
Zinc-dependent T-cell maturation factor (in vitro); anti-inflammatory and antinociceptive effects and improved tumour immunotherapy response (rodent); one 3-patient human case series
Dosing reference
- Research dose
- 1 to 10 mcg daily (vendor/community range, no published human dose)
- Range
- 1 to 10 mcg, 1x daily
- Reconstitution
- 2 mL bacteriostatic water
- Common vial sizes
- 1 mg
Activity depends on bound zinc at a 1:1 molar ratio; the metal-free peptide is inactive in the rosette assay (Dardenne et al., 1982). No human dosing protocol exists. The single human report gave synthetic FTS intravenously to three immunodeficient children, with immunological gains that regressed when dosing was interrupted (Bordigoni et al., 1982). Rodent central dosing used 0.1 to 1 mcg intracerebroventricularly (Safieh-Garabedian et al., 2003). The low-microgram range in circulation is community convention, not a tested dose.
Mechanism
Thymulin is a nonapeptide first purified from pig serum as facteur thymique serique and sequenced in 1977 (Dardenne et al., 1977; Pleau et al., 1977). Its activity depends on bound zinc: removing metal ions with a chelating resin abolished activity in the rosette assay, and zinc restored it best at a 1:1 metal-to-peptide ratio, which is why the active zinc-bound form carries the name thymulin (Dardenne et al., 1982). Plasma levels track thymic function across life, peaking in childhood and falling from adolescence (Consolini et al., 2000). In rodents, thymulin and its peptide analog are anti-inflammatory and antinociceptive in the central nervous system (Safieh-Garabedian et al., 2003). Recent mouse work identifies suppression of NF-kappaB-driven cytokine production by pro-inflammatory myeloid cells as a mechanism (Kanemaru et al., 2026).
Evidence
Preclinical: animal or in vitro data only
- The circulating thymic factor was purified from pig serum and sequenced as pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn; synthetic peptide reproduced the biological activity (Dardenne et al., 1977; Pleau et al., 1977)
- Chelating metal ions abolished activity and zinc restored it at a 1:1 molar ratio, which is why the active form was renamed thymulin (FTS-Zn) (Dardenne et al., 1982)
- Three immunodeficient children given synthetic FTS intravenously showed improved cell-mediated immunity tests and the appearance of serum IgA, which regressed when dosing stopped and returned when it restarted (Bordigoni et al., 1982)
- Plasma thymulin is detectable at birth, peaks at 5 to 10 years, falls from adolescence and reaches its lowest level by about 36 years in 93 healthy individuals (Consolini et al., 2000)
- Intracerebroventricular pretreatment in rats reduced endotoxin-induced hyperalgesia dose-dependently and altered brain cytokine levels (Safieh-Garabedian et al., 2003)
- Human-trial status: no randomised trial of thymulin exists. The only human dosing report is a 3-patient case series from 1982. Recent work is preclinical: thymulin suppressed age-associated myeloid inflammation and improved tumour control in mice (Kanemaru et al., 2026)
References
- Structural study of circulating thymic factor: a peptide isolated from pig serum. II. Amino acid sequence. Pleau JM, Dardenne M, Blouquit Y, Bach JF, Journal of Biological Chemistry, 1977
- Contribution of zinc and other metals to the biological activity of the serum thymic factor. Dardenne M, Pleau JM, Nabarra B, et al., Proceedings of the National Academy of Sciences, 1982
- Improvement of cellular immunity and IgA production in immunodeficient children after treatment with synthetic serum thymic factor (FTS). Bordigoni P, Faure G, Bene MC, Dardenne M, Bach JF, Duheille J, Olive D, The Lancet, 1982
- Distribution of age-related thymulin titres in normal subjects through the course of life. Consolini R, Legitimo A, Calleri A, Milani M, Clinical and Experimental Immunology, 2000
- Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection. Safieh-Garabedian B, Ochoa-Chaar CI, Poole S, et al., Neuroscience, 2003
- Physiology and therapeutic potential of the thymic peptide thymulin. Reggiani PC, Schwerdt JI, Console GM, et al., Current Pharmaceutical Design, 2014
- Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy. Kanemaru H, Luong S, Yamamoto Y, Mizukami Y, Ito F, Nature Communications, 2026
Side effects
There is no safety dataset. The only human report is three immunodeficient children given intravenous synthetic FTS in 1982, which describes immunological changes and no adverse events (Bordigoni et al., 1982). No trial, no repeat-dose study and no pharmacokinetics exist in any species at a dose relevant to use. Because it modifies T-cell function, caution is warranted in autoimmune disease and with immunosuppressive therapy; that is mechanistic, not observed.
Storage
- Storage
- Refrigerate 2-8°C (36-46°F)
- Lyophilized
- 2+ years at room temp, 3+ years refrigerated
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- Not measured. No pharmacokinetic study of thymulin exists in any species.
- Bioavailability
- Not measured by any route. Human and rodent dosing used intravenous or intracerebroventricular administration; activity requires bound zinc (Dardenne et al., 1982; Bordigoni et al., 1982).
- Molecular weight
- 858.9 Da
- Sequence
- [pGlu]AKSQGGSN (zinc-bound form is the active one)