Protocols · Immune
Thymalin dosage protocol
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Thymalin: research background
What Thymalin Is
Thymalin is an immunomodulatory drug that contains a polypeptide extract derived from the thymus (PMID 37686182, PMID 33237528). It is a complex peptide preparation (PMID 12374906). The active substances of Thymalin include the dipeptides KE and EW (PMID 37686182). KE is reported to stimulate cellular immunity and nonspecific resistance, activating macrophages, blood lymphocytes, thymocytes, and neutrophils (PMID 37686182). EW is reported to reduce angiotensin-induced vasoconstriction and preserve endothelium-dependent vascular relaxation by inhibiting ACE2 (PMID 37686182).
How it is Thought to Work
Thymalin regulates immune system functions (PMID 33237528). It is thought to increase the functional activity of T lymphocytes (PMID 33237528). In human hematopoietic stem cells (HSC) in vitro, Thymalin reduced the expression of CD44 (a stem cell marker) and CD117 (a molecule of an intermediate stage of HSC differentiation) by 2-3 times, while increasing the expression of CD28 (a marker of mature T lymphocytes) by 6.8 times. This suggests it stimulated the differentiation of CD117+ cells into mature CD28+ T lymphocytes (PMID 33237528). The specific mechanisms of its immunomodulatory action during conditions like COVID-19 are still under investigation (PMID 37686182).
What Laboratory and Animal Studies Report
Thymalin has shown anticarcinogenic effects in various experimental models (animal studies) (PMID 12374906). In rats with transplanted sarcoma 45, Thymalin in doses lower than therapeutic doses led to tumor growth arrest and regression in over half of the animals, and suppressed growth by 78% in others. This was accompanied by increased lymphoproliferative activity and tissue basophils and plasmocytes in the thymus (animal study) (PMID 29797130). Thymalin stimulates immunity (animal studies) (PMID 12374906). In rats, injecting Thymalin into soft tissues surrounding a mandible bone defect, along with a hydroxyapatite bone graft, stimulated reparative osteogenesis. This involved rapid cleaning of the defect, reduced neutrophils, increased monocytes, macrophages, and lymphocytes, and activated hematopoietic processes and bone tissue mineralization (animal study) (PMID 38431810). This animal study also showed an increase in T-lymphocytes, B-lymphocytes, and macrophages, and changes in macrophage phenotypes (decreased M1, increased M2) in the post-traumatic regenerate (animal study) (PMID 38642352).
Human Evidence So Far
Among the effects of Thymalin, its ability to stimulate immunity is prominent (PMID 12374906). It has been assessed clinically for geroprotective effects in 266 elderly and older persons, showing an ability to normalize basic human organism functions, including cardiovascular, endocrine, immune, and nervous systems, homeostasis, and metabolism (human study) (PMID 12577695). Restoration of homeostasis was associated with a 2.0-2.4-fold decrease in acute respiratory disease incidence and reduced incidence of ischemic heart disease, hypertension, deforming osteoarthrosis, and osteoporosis (human study) (PMID 12577695). A human study showed a 2.0-2.1-fold decrease in mortality rate among Thymalin-treated patients over 6-8 years compared to a control group, and a 4.1-fold decrease when Thymalin was combined with Epithalamin annually for 6 years (human study) (PMID 12577695). Thymalin has demonstrated efficacy in treating acute respiratory distress syndrome, chronic obstructive pulmonary disease, and in complex therapy for severe COVID-19 in middle-aged and elderly patients (human study) (PMID 37686182). In severe COVID-19 patients, Thymalin increased lymphocytes and monocytes by 2 times, leukocytes by 1.3 times, and platelets by 1.5 times. It also decreased platelet/lymphocyte and neutrophil/lymphocyte ratios by 1.4 times and 2 times, respectively. Thymalin reduced fibrinogen, lactate dehydrogenase, and D-dimer levels by 1.2, 1.8, and 1.7 times respectively, and was associated with a hospital mortality of 20.6% compared to 40.9% in standard therapy and 28.4% with Tocilizumab (human study) (PMID 36169363).
Open Questions and Limitations
While Thymalin has demonstrated efficacy in certain conditions, the precise mechanism of its immunomodulatory action, particularly in contexts like COVID-19, is not fully clear (PMID 37686182). Further study is needed to understand the targeted molecular mechanism of its biological activity (PMID 33237528). The observation of decreased CD28+, CD4+, and CD8+ T lymphocytes in severe COVID-19 patients suggests that the antiviral effect of Thymalin may involve compensatory stimulation of HSC differentiation into CD28+ T lymphocytes when immunity is suppressed (PMID 33237528).
Key Terms Explained
Geroprotector activity refers to the ability to protect against or slow down age-related changes and conditions (PMID 12374906, PMID 12577695). Homeostasis is the ability of an organism to maintain stable internal conditions (PMID 12577695). Immunomodulatory means affecting or regulating the immune system (PMID 37686182, PMID 33237528). Reparative osteogenesis is the process of bone repair and regeneration (PMID 38431810). Hematopoietic stem cells (HSC) are cells that can develop into all types of blood cells, including immune cells (PMID 33237528). T lymphocytes (T cells) are a type of white blood cell critical to the immune system (PMID 33237528). CD28 is a protein marker found on T lymphocytes (PMID 33237528). CD44 and CD117 are markers associated with stem cells and intermediate stages of differentiation (PMID 33237528). M1 and M2 macrophages are different types of immune cells with distinct functions (PMID 38642352).
Studies cited in this section
- Peptides and Ageing. — Neuro endocrinology letters, 2002 (PMID 12374906)
- [Geroprotective effect of thymalin and epithalamin]. — Advances in gerontology = Uspekhi gerontologii, 2002 (PMID 12577695)
- The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19. — International journal of molecular sciences, 2023 (PMID 37686182)
- Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study. — Wiadomosci lekarskie (Warsaw, Poland : 1960), 2024 (PMID 38431810)
- Expression features of T-lymphocytes, B-lymphocytes and macrophages in the post-traumatic regenerate of the mandible rats under conditions of filling a bone defect with hydroxyapatite-containing osteotropic material and thymalin injecting the surrounding soft tissues. — Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2024 (PMID 38642352)
- Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo. — Bulletin of experimental biology and medicine, 2018 (PMID 29797130)
- [Morphological compound and indicators of the blood clotting system in severe COVID-19 patients of middle aged and elderly during treatment of Tocilizumab and Thymalin.]. — Advances in gerontology = Uspekhi gerontologii, 2022 (PMID 36169363)
- Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. — Bulletin of experimental biology and medicine, 2020 (PMID 33237528)
Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.
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