Immunoregulatory effects of fraction 5 thymus peptides. I. Thymosin α1 enhances while thymosin β4 suppresses the human autologous and allogeneic mixed lymphocyte reaction

Baxevanis, Constantin N.; Reclos, George J.; Perez, Sonia A.; Kokkinopoulos, D.; Papamichail, Michail

doi:10.1016/0162-3109(87)90050-6

Cited by 43 publications

(14 citation statements)

References 18 publications

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“…Ttx, is an acidic peptide (mol wt = 3,108) that has shown activity similar to that of TF5 in modulating the maturation of T cells (15). TF5 and Ta, can influence immunoregulatory T cell function; promote IFN-a, IFN-y and IL2 production by human lymphocytes; and increase lymphocyte IL2 receptor expression (16)(17)(18)(19)(20)(21).…”

Section: /1/31239mentioning

confidence: 99%

Thymosin treatment of chronic hepatitis B: A placebo-controlled pilot trial

et al. 1991

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Chronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin-alpha 1 in a prospective, placebo-controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin-alpha 1 and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin-treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p less than 0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo-treated patients but in only one of seven thymosin-treated patients (p less than 0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and in in vitro production of interferon-gamma over initial values. No significant side effects were observed in patients given thymosin or in placebo-treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 +/- 3 mo of follow-up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with chronic viral infection.

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Section: /1/31239mentioning

confidence: 99%

Thymosin treatment of chronic hepatitis B: A placebo-controlled pilot trial

et al. 1991

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“…It is a 43-aminoacid polypeptide that was originally described as a thymic maturation factor (Low et al, 1981). It was reported that Tb4 could suppress the mixed lymphocyte proliferative response, induce the expression of terminal deoxynucleotidyl transferase in T cells, inhibit the migration of macrophages in vitro and induce the phenotypic changes in T cell line (Baxevanis et al, 1987;Kokkinopoulos et al, 1985). Recently, it was reported that Tb4 promotes angiogenesis, wound repair, and hair follicle development (Philp et al, 2004); stimulates tumor metastasis by activating cell migration and angiogenesis (Cha et al, 2003;Liu et al, 2003;Wang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Thymosin β4 and AcSDKP inhibit the proliferation of HL‐60 cells and induce their differentiation and apoptosis

Huang

Wang

2006

Cell Biology International

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Our previous works have shown that bone marrow stromal cells secrete thymosin beta4 (Tbeta4) and AcSDKP. Tbeta4 and AcSDKP are existed in the conditioned medium of bone marrow endothelial cells. They exerted inhibitory effects on hematopoietic cells and then had protective effect on the early hematopoietic cells, which were cultured in the presence of hematopoietic stimulators. Thymosin beta4 consists of 43 peptides with a molecular weight of 4963. It contains at its N-terminal end the sequence of the acetylated tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP). This study was performed to evaluate the effect of Tbeta4 and AcSDKP on the growth of HL-60 cells. It was showed that Tbeta4 (10(-11)-10(-7)mol/L) and AcSDKP (10(-11)-10(-7)mol/L) had the dose-dependent inhibitory effect on the proliferation of HL-60 cells. Based on cell morphology and NBT reduction, Tbeta4 and AcSDKP induced differentiation of HL-60 cells. Morphologic and DNA fragment analysis proved that Tbeta4 and AcSDKP induced apoptosis of HL-60 cells. In order to analyze the mechanism of the effects of Tbeta4 and AcSDKP, intracellular free Ca(2+) concentration ([Ca(2+)](i)) of HL-60 leukemic cells was tested and Atlas cDNA Expression Array was performed. The results showed that Tbeta4 and AcSDKP could increased [Ca(2+)](i) by stimulating the release of Ca(2+) from intracellular Ca(2+) pool. Moreover, AcSDKP could also elicit a potent extracelluar calcium influx in HL-60 cells. Tbeta4 could also change apoptotic-related gene expression in leukemic cells, and resulted in the inhibition of proliferation and induction of differentiation and apoptosis of leukemic cells.

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“…Thymosin-β4 was first isolated from calf thymosin fraction 5; it is also found in various organs such as the spleen, thymus, liver that exhibit biological activity on the immune system cells. Thymosin-β4 has been reported to suppress the mixed lymphocyte proliferative response, 14 induce the expression of terminal deoxynucleotidyl transferase in T cells, 15 inhibit the migration of macrophages in vitro, 16 and inhibit cytokine production by neutrophils after tumor necrosis factor (TNF)-α stimulation. 17 TGF-β, which can be released by thymocyte and thymic epithelial cells, almost inhibits all lymphocyte proliferation, including mitogen-and allogenic antigen-induced T-cell proliferation and Staphylococcus aureus Cowan I (SAC)-induced and IL-2 independent B-cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Acute Electrical Stimulation of Nucleus Ambiguus Enhances Immune Function in Rats

Mei¹,

Yang²,

Wang³

et al. 2008

Can. j. neurol. sci.

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It is well known that there exists bidirectional regulation in the central nervous system (CNS) and immune system. [1][2][3] The CNS can have a widespread effect on the immune system following the activation of the hypothalamic-pituitary-adrenal axis 4,5 and the sympathetic nervous system. 3,6,7 Thus far, many regions in the brain such as the hypothalamic nuclei, brain reward system, limbic structures, cortex, midbrain periaqueductal gray matter, cerebellum, circumventricular organs, and vagal complex have been identified as "immunoactive" areas. 8 The nucleus ambiguous (Amb), that is a nucleus of the vagus nerve, is located in the ventrolateral reticulate structure of the medulla oblongata. Thus far, probably owing to traditional ideas regarding this area, study of the Amb ABSTRACT: Background: Up to now, many ''immunoactive'' brain areas have been identified, such as hypothalamic nuclei, brain reward system; but the nucleus ambiguous (Amb), a nucleus nervi vagis of medulla oblongata, was less well studied in neuroimmunomodulation. Methods: In order to obtain more profound comprehension and more knowledge on Amb, we studied the effect of acute electrical stimulation of Amb on thymus and spleen activity in rat. A stimulator was applied to stimulate the Amb of the anaesthetic rats using the parameter at 100μA×5ms ×100 Hz every 1s for 1 min. The levels of TGF-β and thymosin-β4 mRNA in thymus, the release of IL-2 and IL-6 at splenocyte in vitro and splenic lymphocyte proliferation were measured at hour 0.5,1,2,3 following the electrical stimulation. Results: The results showed that concanavalin A (Con A)-induced splenic lymphocyte proliferation and the release of IL-2 and IL-6 were all significantly enhanced at 0.5, 1, and 2 h following effective Amb stimulation as compared to in the control group. However, as compared to in the control group, the levels of TGF-β and thymosin-β4 mRNA in the thymus were both remarkably reduced at 0.5, 1, and 2 h following effective Amb stimulation. Conclusions: These findings reveal that the Amb participates in the modulation of animal immune functions.RÉSUMÉ: La stimulation électrique aiguë du noyau ambigu stimule la fonction immunitaire chez le rat. Contexte : Plusieurs zones immunoactives du cerveau ont été identifiées jusqu'à maintenant, dont les noyaux hypothalamiques (corps de Luys, noyau sous-thalamique), le système de récompense du cerveau. Cependant, il existe peu d'études sur le rôle du noyau ambigu (Amb), le noyau du nerf vague situé dans le bulbe rachidien, dans la neuro-immunomodulation. Méthodes

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Immunoregulatory effects of fraction 5 thymus peptides. I. Thymosin α1 enhances while thymosin β4 suppresses the human autologous and allogeneic mixed lymphocyte reaction

Cited by 43 publications

References 18 publications

Thymosin treatment of chronic hepatitis B: A placebo-controlled pilot trial

Thymosin treatment of chronic hepatitis B: A placebo-controlled pilot trial

Thymosin β4 and AcSDKP inhibit the proliferation of HL‐60 cells and induce their differentiation and apoptosis

Acute Electrical Stimulation of Nucleus Ambiguus Enhances Immune Function in Rats

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