Thymic Peptides

Josef Beuth

General Remarks

In 1965, Angelo Mario DiGeorge observed a congenital immune defect with pronounced T lymphocytopenia. This defect was associated with thymic hypoplasia caused by malformation of the third and fourth pharyngeal pouches due to disturbed embryonic development during the twelfth week of pregnancy (DiGeorge syndrome). It soon became clear that the thymus gland represents the key organ in the establishment and functionality of cellular immunity. Its far-reaching tasks include:

– regulation of hematopoiesis in the bone marrow

– differentiation of T lymphocytes (helper T cells developing through specific contacts with major histocompatibility complex [MHC] class II⁺ cells, and cytotoxic T cells developing through specific contacts with MHC class I⁺ cells) as well as their maturation and release

– development of immune tolerance for the body’s own tissues

– secretion of thymic hormones, cytokines, and growth factors (8, 12).

Cytokines and growth factors (colony stimulating factors) control the functions of immune cells and have been recommended for diverse clinical indications. Meanwhile, the initial euphoria over their discovery has been put into perspective by the realization that a multitude of cofactors complicates a therapeutically meaningful application. Thymic peptides, thymic hormones, and thymic cytokines finally received increasing attention in the context of experimental and clinical evaluation of cytokines and growth factors. Promising biological activities and pharmacological effects of thymus peptides were described, thus leading to an increase in preclinical research.

For purposes of this discussion we distinguish between:

– total thymic extracts

– thymic peptides

– standardized thymic peptide mixtures (1, 2, 6, 8, 9, 12).

Total Thymic Extracts (Complex Mixtures)

Data on the preclinical efficacy of total thymic extracts are not available in scientific databases (e. g., MEDLINE). The multitude of published data—in nonpeer-reviewed journals, mostly published or sponsored by product manufacturers—does not prove the scientific relevance of total thymic extracts.

Thymic Peptides

Thymic peptides have properties that can restore and stimulate the immune system. It has been shown that the activity of natural killer (NK) cells against tumor cells, which is suppressed in cancer patients, can be significantly increased in vitro. In addition to this restoring or activating activity, there is evidence that thymic peptides influence the cytokine balance. It has been demonstrated experimentally that preparations of thymic peptides induce the release of interleukin-8 and monocyte chemotactic protein-1 (MCP-1), both of which act as cytokines that enhance the anticancer activity of monocytes.

Standardized Thymic Peptide Mixtures

Some effects of standardized thymus peptide mixtures have been well documented in oncology. They include:

– restoration and stimulation of immune cells in case of immunosuppression due to therapy or cancer

– increase in cell numbers and activity of T lymphocytes, NK cells, and LAK cells (lymphokine-activated killer cells)

– compensation of undesired drug effects and, especially, of tumor-destructive radiation therapy or chemotherapy

– activation of the neuroendocrine network

Table 16.1 Total thymic extracts and relevant thymic peptides (examples)

	Molecular weight (Da)**	Constituents
I Complex mixtures Total thymic extract (THX)		Proteins, peptides, amino acids
II Low molecular weight mixtures Thym Uvocal* Thymoject	< 5 000 < 10 000	Protein-free, chromatographically standardized peptide mixtures
III Thymic fractions Thymic humoral factor Thymosin fraction V	< 3 400 < 12 000	Biochemically characterized, synthetic Biochemically characterized
IV Thymic peptides Thymopentin Thymosin α−1 Thymopoietin II	680 3 100 5 600	Pentapeptide Polypeptide Polypeptide

*Pharmaceutical and biological qualities, including BSE security, certified by the BfArM (Germany).

**DA = Daltons

Table 16.2 Experimental in-vitro and in-vivo data on the effects of standardized thymic peptide mixtures (a), thymosin α−1 (b), and thymic humoral factor (c)

In vitro	In vivo (murine models)
↑Immunocyte activity (a, b, c)	↑Immunocyte number/activity in peripheral blood (a, b, c)
↑Cytokine release (a, b, c)	↑Thymocyte proliferation (a, b, c)
↑Proliferation, maturation, and differentiation of thymocytes (a, b, c) and bone marrow progenitor cells (b)	↑Anticancer/antimetastatic activity (a, b, c)
↑Antiviral activity (b)	↑Immunocyte restoration (b, c)