Modulatory role of thymosin-alpha-1 in normal bone-marrow haematopoiesis and its effect on myelosuppression in T-cell lymphoma bearing mice.
Paul. Saki S; Sodhi. Ajit A
Key Findings
- Thymosin‑alpha‑1 increased proliferation of normal mouse bone‑marrow cells in vitro, with the strongest effect at 100 ng/ml.
- It enhanced the number and size of myeloid colonies, and this effect was amplified by colony‑stimulating factors like M‑CSF, G‑CSF, GM‑CSF, and IL‑3.
- In mice bearing T‑cell lymphoma, which normally reduces bone‑marrow activity, thymosin‑alpha‑1 restored cell proliferation and colony formation after a single 10 µg injection.
Practical Outcomes
- The data suggest thymosin‑alpha‑1 could support blood‑cell production and counteract bone‑marrow suppression in disease models, but it’s only been shown in mice. No human dosing or safety information is available, so it isn’t ready for self‑experimentation. Keep an eye on clinical studies before considering it for personal protocols.
Summary
In mice, the peptide thymosin‑alpha‑1 helped bone‑marrow cells grow and form more blood‑cell colonies, even when the animals had a T‑cell lymphoma that normally suppresses bone‑marrow activity. A single injection (10 µg per mouse) or a lab dose of 100 ng/ml gave the biggest boost, especially when combined with other growth factors.
Abstract
In continuation with the earlier and ongoing studies on Thymosin-alpha-1 (Talpha1) exerting its immunomodulatory effects on various components of the immune system including T-cells, NK-cells, blood lymphocytes and macrophages, the role of Talpha1 in normal bone-marrow haematopoiesis has been investigated in the present study. The haematopoietic alterations associated with the growth of murine T-cell lymphoma, Dalton's Lymphoma (DL) and subsequently its restoration by Talpha1 was also investigated. It is observed that the non-adherent bone-marrow cells from normal mice (N-BMCs) exhibited enhanced proliferation on in vitro treatment with Talpha1 (dose range of 1-100 ng/ml) with maximal response at 100 ng/ml of Talpha1. In vitro stimulation with 100 ng/ml of Talpha1 also resulted in increased myeloid colony formation, as manifested by the rise in total number of colonies, frequency of the individual colony types and their size. This response was further upregulated in the presence of various colony stimulating factors (CSFs) like MCSF, GMCSF, GCSF and IL-3. Similarly, in vivo administration of Talpha1 (a single intraperitoneal injection of 10 microg per mouse) to normal mice also resulted in enhanced proliferation and colony formation by BMCs as compared with BMCs obtained from untreated mice. On the contrary, the progressive growth of T-cell lymphoma in mice led to suppressed myelogenesis, with marked reduction in the total colony numbers and their size. The BMCs from DL-bearing mice (DL-BMCs) displayed a preferential lineage-restricted differentiation towards the granulocytic-type colonies with maximum numbers of CFU-Gs and CFU-GMs, followed by CFU-Ms. However, incubation of DL-BMCs with 100 ng/ml of Talpha1, in vitro restored their suppressed proliferation and colony forming ability (CFA) with significantly enhanced total number of colonies and individual colony types, which further increased in the presence of CSFs. In vivo studies with BMCs from DL-bearing mice treated with single intraperitoneal injection of 10 microg Talpha1/mouse also resulted in significant enhancement in their proliferative as well as colony forming ability in comparison to that of untreated DL-mice. The present observations suggest that Talpha1 can positively modulate the haematopoietic functions of normal murine BMCs, in addition to its myelorestorative role in tumour-bearing mice showing suppressed myelopoiesis.
Study Information
pubmed
2002
2002-07-03T00:00:00.000Z
10.1016/s0165-2478(02)00046-9