This study aimed to investigate the regulatory effect and mechanism of thymopentin on the growth of subcutaneous hepatocellular carcinoma in mice. A subcutaneous tumor model of Hepa1-6 liver cancer in immunocompetent mice was constructed, with three randomly divided groups based on tumor volume: control group, low-dose thymopentin (TP5) group (10 mg/kg), and high-dose TP5 group (20 mg/kg), with 6 mice in each group. Drugs were administered, and the intervention effect of thymopentin on tumor growth was evaluated. Hepa1-6 cells were then cultured in vitro and treated with blank medium and TP5 of different concentrations (10, 100, 1000 ng/mL) for 72 hours. Cell viability was detected by sulforhodamine B (SRB) colorimetry. A subcutaneous tumor model of liver cancer LM3 in immunocompromised mice was constructed, with three randomly divided groups based on tumor volume: control group, TP5 group (20 mg/kg), and positive drug Sorafinib group (30 mg/kg). The intervention effect of thymopentin on the growth of subcutaneous tumors in immunocompromised mice was evaluated. Flow cytometry was used to analyze the changes in the proportion of T cells and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment 11 days after TP5 administration in the Hepa1-6 model. MDSCs were cultured in vitro and treated with TP5. The effect of TP5 on MDSCs was evaluated by detecting the levels of ROS, IL-6, and NO, which are effector molecules of MDSCs. The mouse subcutaneous liver cancer model was established again using C57BL/6N mice. After 10 days, they were randomly divided into four groups based on tumor volume: control group, low-dose TP5 group (10 mg/kg), high-dose TP5 group (20 mg/kg), and arginine-deficient TP5 group (15 mg/kg). Drugs were administered continuously for 11 days, and the intervention effect of arginine-deficient TP5 on tumor growth was evaluated based on tumor weight. Annexin-V staining was used to detect the impact of TP5 on T cell survival. The results showed that both low and high doses of TP5 inhibited the growth of subcutaneous liver cancer in immunocompetent mice (P < 0.05), yet TP5 had no direct inhibitory effect on the proliferation of tumor cells cultured in vitro. Besides, a high dose of TP5 could not inhibit the growth of subcutaneous liver cancer in immunocompromised mice. Furthermore, TP5 promoted the infiltration of CD4 and CD8 T cells but decreased MDSCs in the subcutaneous tumor microenvironment of immunocompetent mice. TP5 did not affect the levels of ROS, IL-6, and NO in MDSCs. Lastly, arginine-deficient TP5 could not inhibit the growth of subcutaneous liver cancer in immunocompetent mice. Accordingly, TP5 but not arginine-deficient TP5 promoted the increase in the proportion of viable CD4 and CD8 T cells cultured in vitro. These results suggest that TP5 may inhibit the growth of liver cancer by increasing T cell number in the liver cancer microenvironment.
thymopentin ; hepatocellular carcinoma ; tumor microenvironment ; arginine ; T cells

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.
Adjuvants, Immunologic ; pharmacology ; Animals ; Antibodies, Viral ; blood ; Cell Proliferation ; drug effects ; Influenza A Virus, H9N2 Subtype ; drug effects ; physiology ; Influenza Vaccines ; immunology ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Lymphocytes ; drug effects ; Mice ; Oligopeptides ; immunology ; Orthomyxoviridae Infections ; drug therapy ; Recombinant Fusion Proteins ; immunology ; Spleen ; cytology ; Thymopentin ; immunology ; Thymus Gland ; cytology ; Vaccines, Inactivated ; immunology ; Virus Replication

Acupuncture Points ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Respiratory Tract Infections ; drug therapy ; Thymopentin ; administration & dosage

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.
Adjuvants, Immunologic ; administration & dosage ; pharmacokinetics ; Animals ; Area Under Curve ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Glucose ; chemistry ; Liposomes ; chemistry ; Male ; Particle Size ; Phosphatidylcholines ; chemistry ; Phosphatidylglycerols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Thymopentin ; administration & dosage ; pharmacokinetics ; Triolein ; chemistry

OBJECTIVETo evaluate the efficacy and safety of high doses of thymopentin (10 mg/d) combined with transartery chemoembolization for primary liver cancer.

METHODSFifty 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.

RESULTSThere 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.

CONCLUSIONTransartery 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.

Adjuvants, Immunologic ; adverse effects ; therapeutic use ; Adult ; Aged ; Asthenia ; chemically induced ; CD4-Positive T-Lymphocytes ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Disease-Free Survival ; Epirubicin ; administration & dosage ; Female ; Fever ; chemically induced ; Fluorouracil ; administration & dosage ; Humans ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; therapy ; Lymphocyte Count ; Male ; Middle Aged ; Nausea ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; Remission Induction ; Survival Rate ; Thymopentin ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo explore the efficacy of anti-viral drug in combination with immunoregulatory agent in treatment of chronic hepatitis B.

METHODSTotally 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.

RESULTSAt 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.

CONCLUSIONSLamivudine in combination with thymopentin can exert great and lasting effects on HBV and is effective in normalization of ALT.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Thymopentin ; therapeutic use ; Treatment Outcome

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.
Dermatitis, Atopic* ; Eosinophils ; Hematocrit ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunomodulation ; Injections, Subcutaneous ; Lymphocytes ; Neutrophils ; Skin Diseases ; Thymopentin*

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.
Body Surface Area ; Dermatitis, Atopic* ; Humans ; Injections, Subcutaneous ; Thymopentin*

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.
Abscess ; Child ; Dermatitis ; Eczema ; Eosinophilia ; Female ; Humans ; Immunoglobulin E ; Job Syndrome ; Neutrophils ; Pneumonia, Staphylococcal ; Skin ; Thymopentin*

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.
Acyclovir ; Adult ; Appointments and Schedules ; Autoimmune Diseases ; Erythema Multiforme* ; Erythema* ; Follow-Up Studies ; Heme ; Humans ; Injections, Subcutaneous ; Recurrence ; Thymocytes ; Thymopentin*