Expression and adjuvant effects of the fusion peptide TBP5 / 生物工程学报

Thymopentin (TP5) and bursopentin (BP5) are both immunopotentiators. To explore whether the TP5-BP5 fusion peptide (TBP5) has adjuvant activity or not, we cloned the TBP5 gene and confirmed that the TBP5 gene in a recombinant prokaryotic expression plasmid was successfully expressed in Escherichia coli BL21. TBP5 significantly promoted the proliferation of thymic and splenic lymphocytes of mice. The potential adjuvant activity of the TBP5 was examined in mice by coinjecting TBP5 and H9N2 avian influenza virus (AIV) inactivated vaccine. HI antibody titers, HA antibodies and cytokines levels (IL-4 and IFN-γ) were determined. We found that TBP5 markedly elevated serum HI titers and HA antibody levels, induced the secretion of both IL-4 and IFN-γ cytokines. Furthermore, virus challenge experiments confirmed that TBP5 contributed to inhibition replication of the virus [H9N2 AIV (A/chicken/Jiangsu/NJ07/05)] from mouse lungs. Altogether, these findings suggest that TBP5 may be an effective adjuvant for avian vaccine and that this study provides a reference for further research on new vaccine adjuvants.

Preparation of sustained release multivesicular liposome for thymopentin and preliminary study on its pharmacokinetics in rats / 药学学报

To optimize the formulation and preparation method of multivesicular liposome of thymopentin and to investigate its pharmacokinetics in rats, the multivesicular liposome of thymopentin was prepared by double emulsification method and the formulation was optimized by orthogonal design. The release characteristics of thymopentin from multivesicular liposome in PBS (pH 7.4) and in plasma were investigated. The multivesicular liposome of thymopentin labeled with fluorescein isothiocyanate was prepared by double emulsification method. Its pharmacokinetics was evaluated following intramuscular injection in rats. The optimal formulation of multivesicular liposome of thymopentin were formulated with 7.5% glucose in aqueous phase and 2.25 mol x L(-1) triolein, 2.68 mol x L(-1) DPPG and 16.96 mol x L(-1) DOPC in organic phase. The entrapment efficiency of the multivesicular liposome of thymopentin was above 85% and the mean particle size was about 22 microm. The in vitro release of thymopentin from multivesicular liposome in PBS (pH 7.4) and in plasma was found to be in a sustained manner. The release curves were fitted to Higuchi equation. The pharmacokinetics following intramuscular injection of the multivesicular liposome of thymopentin labeled with fluorescein isothiocyanate in rats showed that the peak concentration of thymopentin was lower and elimination of it was slower significantly than that of thymopentin labeled with fluorescein isothiocyanate solution in the same dose. The plasma concentration of thymopentin maintained above quantitative limitation at 120 h after administration of multivesicular liposome of thymopentin. The optimized formulation and preparation technology of multivesicular liposome of thymopentin with higher entrapment efficiency are feasible with good reproducibility. Multivesicular liposome of thymopentin showed significant sustained-release property following intramuscular injection in rats.

Study on the efficacy and safety of high dose thymopentin combined with trans-artery chemoembolization for primary liver cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of high doses of thymopentin (10 mg/d) combined with transartery chemoembolization for primary liver cancer.</p><p><b>METHODS</b>Fifty primary liver cancer patients were randomly divided into two groups: therapeutic and control group, and all were treated with transfemoral artery chemoembolization (TACE) with oxaliplatin 150 mg, pharmorubicin 50 mg, 5-Fu 750 mg, CF 300 mg and lipiodol 20 ml. Therapeutic group (25) were added 10 mg thymopentin daily after TACE: i.v. on dl - d5, and im on D6 - D21.</p><p><b>RESULTS</b>There was a significant difference in adverse effect and toxicity such as naupathia,fever, swirl, asthenia observed between two groups (P < 0.05). No difference in either pre- or post-chemotherapy peripheral blood examination and biochemical assay was found between two groups (P > 0.05). In control group, CD4+ cell was 37.92% +/- 8.71% in pre-treatment, which decreased to 29.16% +/- 8.21% in post-treatment with a significant difference (P < 0.01), whereas there was no evident difference in CD4+ cell between pre-treatment and post-treatment in the treatment group.</p><p><b>CONCLUSION</b>Transartery chemoembolization combined with high dose of thymopentin in the treatment for primary liver cancer is effective and safe, and can significantly improve the immune function and the chemotherapy tolerance.</p>

Therapeutic effects of Lamivudine in combination with Thymopentin on chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of anti-viral drug in combination with immunoregulatory agent in treatment of chronic hepatitis B.</p><p><b>METHODS</b>Totally 98 patients with chronic hepatitis B were divided at random into 3 groups. In groups A (42 cases) lamivudine was used in combination with thymopentin to treat chronic hepatitis B. Lamivudine or thymopentin was used alone in groups B (38 cases) and C (18 cases), respectively. The dynamic changes in serum parameters reflecting HBV replication and liver function were observed.</p><p><b>RESULTS</b>At the end of the treatments, the rates of negative conversion of HBeA g and positive conversion of anti-HBe in the serum were significantly higher in group A than in group B (P<0.05). There was no significant difference between group A and group C (P>0.05). The rate of negative conversion of HBV DNA was markedly higher in group A than in group C (P<0.05). However, there was no remarkable difference between group A and group B (P>0.05). The changes in parameters of viral replication in 6 and 12 months after the treatments were not significantly different from those at the end of the treatments. The effective rate and total effective rate were markedly higher in group A than in the ther 2 groups. Meanwhile, the rate of ALT normalization of remained higher than 85% in group A.</p><p><b>CONCLUSIONS</b>Lamivudine in combination with thymopentin can exert great and lasting effects on HBV and is effective in normalization of ALT.</p>

The efficacy of thymopentin in the treatment of atopic dermatitis / 천식및알레르기

BACKGROUND: Thymopentin(TP-5) is an immunomodulatory agent which may be a promising new drug in the treatment of patients with severe atopic dermatitis. OBJECTIVE: The aim of this study was to evaluate the efficacy of thymopentin for treatment of severe atopic dermatitis. MATERIAL AND METHOD: Fifteen patients with severe atopic dermatitis received subcutaneous injections of 50mg thymopentin three times per week for 6 weeks. Clinical extent and severity parameters were assessed at baseline, at regular intervals during therapy and 4 weeks posttherapy. Use of antihistamine and topical steroid were permitted. RESULT: Significant reduction in severity scores and body surface area involvement was observed and no significant side effects were noted(p<0.05). CONCLUSION: Thymopentin may be considered to be an effective adjunctive therapeutic agent in the treatment of severe atopic dermatitis. Further studies will be needed to determine the action mechanism of thymopentin.

Thymopentin Therapy in Atopic Dermatitis

PURPOSE: Atopic dermatitis is a chronic relapsing inflammatory skin disease that results from allergic reaction. Steroid therapy has become a major therapeutic modality for treatment of atopic dermatitis. Several immunomodulatory therapies have been tried for atopic dermatitis. In this study thymopentin therapy was performed and its clinical effects and laboratory results were evaluated. METHODS: Atopic dermatitis with typical clinical symptoms were included in this study. Twelve patients were treated with subcutaneous injection of thymopentin ( (Imupentin ) at a dose of 1 mg/kg, three times per week for eight weeks. Clinical scores were measured by Hanifin scoring system before and at the end of the treatment. General hematologic laboratory tests such as hemoglobin, hematocrit, WBC count, neutrophil percentage, lymphocytes percentage and eosinophil percentage as well as blood IgE level were conducted at the same time. RESULTS: The clinical severity of atopic dermatitis patients was markedly improved by thymopentin therapy. The clinical severity score improved by 85.5%. Three patients showed complete remission of clinical status at the end of thymopentin therapy. Hemoglobin, hematocrit, WBC counts, neutrophil percentage, and lymphocyte percentage were not affected by the thymopentin therapy. Eosinophil percentage and blood IgE level were significantly reduced statistically. CONCLUSION: Thymopentin therapy is an effective immunomodulatory therapeutic modality in atopic dermatitis. Thymopentin decreased eosinophil percentage and blood IgE levels without other hematologic changes.

Vaccine adjuvants: A new hope for effective immunization

Two important issue regarding the use of immunization to control infections and malignancies in the futureare: 1) the need to render poorly immunogenic, often highly purified, antigens more effective; and 2) the desire to direct the immune response in specific ways to achieve the most relevant response for each disease. The first issue can be solved by a broad range of vaccine adjuvants. The second requires careful selection among the adjuvants to allow directing of the immune response in the most appropriate manner. For exemple, in different settings expansion of a B cell response, cytotoxic T cell response, or enhancement of either a Th1 or Th2 subset response may be desired. These goals are accomplished by the use of several newly developed non-cytokine adjuvants, or by direct injection of the relevant cytokines. Some non-cytokine molecular adjuvants and cytokines used as adjuvants have already been proven effective in animal models and/or in clinical trials. Here, we review the present state of art in the use of vaccine adjuvants for control of various infections diseases.

A Case of Job Syndrome-Experience with Thymopentin / 소아알레르기및호흡기학회지

The Job syndrome is a primary immunodeficiency disorder characterized by markedly elevated serum IgE levels, recurrent severe infections of the skin and sinoplmonary tract, including staphylococcal pneumonias, chronic eczematoid dermatitis, coarse facial features, and mild eosinophilia. In 1966, Davis et al discribed two patients with severe eczema, chroic sinopulmonary infections, and recurrent staphylococcal abscesses originally. The reason for immunocompromise in the Job syndrome remains unclear, but a chemotactic defect in neutrophils has been described. We have experienced a case of Job syndrome in a 9-year-old girl who had suffered from severe recurrent multiple infections since 2 month of age. After treatment with thymopentin, she was improved clinically. A brief review of related literature is presented.

Two Cases of Atopic Dermatitis Treated with Thymopentin / 대한피부과학회지

The pat,hogenesis of atopic dermititis(AD) is still undefined. The prominent immunologic abnormalities associated with AD are defective cell-mediated immunity and increased IgE production. Also, the predominant CD4 subset in the skin lesion of AD is a Th2-like. Thymopentin, the active pentapepide of a thymic hormone, promotes differentiation of thymocytes and exhibits immunomodulating function. We experienced 2 case. of severe AD patients who were treated with subcutaneous injection of thymopentin three times a week for 6 weeks or 8 weeks. We compared the effects of cyclosporine A(CsA), FK -506 and thymopentin on the production of IL-2, IL-3, IL-4 and sIL-2R in vitro. In patient 1, there was no clinical response with thymopentin therapy. There was no difference in the serum IgE levels between before and after treatment. The ratio of Th/Ts was increased after treatment. In vitro study, CsA and FK-506 inhibited the production of IL-2, IL-3, IL 4 and sIL-2R, and thymopentin inhibited the production of IL-2, IL-3, IL-4 and sIL-2R. In patient 2, the clinical score of the patient was improved from 15 to 10 after treatment with thymopentin. There was no difference in the serum IgE level. The ratio of Th/Ts was decreased after treatment. In vitro study, the production of IL-2, IL-3 and IL-4 were decreased in lymphocytes added with CsA and FK-506, but the production of sIL-2R was increased by CsA and FK-506. Also, the production of IL-3 and IL-4 were increased in lymphocytes added with thyrnopentin, but the proluction of IL-2 and sIL-2R were increased by thymopentin. Our data suggest that thymopentin could be effective in the treatment of severe AD through the upregulation of Thl-like subset, not via the downregulation of Th2-like subset.

A Case of Herpes - Associated Erythema Multiforme Treated with Thymopentin / 대한피부과학회지

Herpes-associated erythema multiforme(HAEM) is a common subtype of erythema multiforme (EM) which usually develops 1-3 weeks after the recurrent herpetic episodes. The role of HSV in the pathogenesis of EM has not been fully defined. Recent studies, however, suggest that the host immune response to HSV, especially cell-mediated immune mechanism, is critical to the development of HAEM and, based on these findings, a variety of immunomodulating agents have been tried for the treatment of recurrent EM. Thymopentin, an immunomodulator that influences the maturation of thymocyte and mature T cell function, has been used as a therapeutic agent for various autoimmune diseases and recurrent HSV infection. A 37-year-old man with HAEM, who had failed to respond to intermittent acyclovir therapy for about 5 years, was treated with a subcutaneous injection of thymopentin 50mg three times a week for 6 consecutive weeks. The EM lesions were completely cleared 5 weeks after starting the treatment, without any sigrificant side effects. We herein, report a case of HAEM who has been treated with a 6-week schedule of thymopentin therapy and has showed no recurrence for the 6 months of follow-up period.

The Efficacy of Thymopentin Therapy for Prophylactic Use in Recurrent Herpes Simplex Virus Infection

BACKGROUND: Herpes recurrences coincide with changes in the immunologic status of the patient, particularly in respect of cell mediated immunity (CMI),, and it has been represented that thymopentin(TP) induces a wide range of immunoregulatory effects. OBJECTIVE: Relapses of herpes simplex seem to depend on the relationship between the cellular immune mechanisms and the virus in its latent phase, therefore immunomodulatory therapy may represent an alternative approach. In this respect, thymopentin may have the potential to become a valuable drug for prophylactic use in patients with recurrent herpes simplex. METHODS: Patients with moderate to severe herpes simplex(a relapse rate of at least 6 times/year) were treated with subcutaneous injection of thymopentin 50mg three times weekly for 6 consecutive weeks. The study consisted of a 6-week therapy and a subsequent 1 year follow-up on average. RESULTS: Fourteen of sixteen patients with herpes simplex improved as demonstrated by a reduction in the relapse rate, shorter duration of episodes and improvement in symptoms such as itching or pain. Four patients did not experience a relapse for more than 1 year after cessation of therapy. In this study, the duration of the symptom-free period increased and the average number of relapses per year was reduced. CONCLUSION: Thymopentin is a highly effective drug, capable of positively influencing recurrent herpetic episodes and reducing the relapse rate.