Thymopentin (TP-5) prevents lipopolysaccharide-induced neuroinflammation and dopaminergic neuron injury by inhibiting the NF-κB/NLRP3 signaling pathway.

Neuroinflammation plays a pivotal role in neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and stroke, and is accompanied by excessive release of inflammatory cytokines and mediators by activated microglia. Microglial inflammatory response inhibition may be an effective strategy for preventing inflammatory disorders. However, the reciprocal connections between the central nervous system (CNS) and immune system have not been elucidated. Thus far, these links have been proven to mainly involve immuno- and neuropeptides. The pentapeptide thymopentin (TP-5) exerts a significant immunomodulatory effect; however, its antineuroinflammatory effects and underlying mechanism are still unclear. In this study, lipopolysaccharide (LPS) was used to establish an inflammation model, and the therapeutic effect of TP-5 was evaluated. Behavioral tests showed that TP-5 treatment could improve the performance of LPS-treated mice in the open field and pole test, but not hanging wire test. TP-5 also attenuated neuronal lesions in the brains of LPS-treated mice. TP-5 reduced cytotoxicity and morphological changes in activated microglia. Label-free quantitative analysis indicated that the expression of multiple proteins and the activation of associated signaling pathways were altered by TP-5. Moreover, TP-5 could inhibit LPS-induced neuroinflammation in the brain and BV2 microglia and the expression of major genes in the NF-κB/NLRP3 signaling pathway. Additionally, tyrosine hydroxylase (TH) expression downregulation was rescued in the LPS + TP-5 group compared with the LPS group. We conclude that TP-5 exerts neuroprotection by alleviating LPS-induced inflammatory damage and dopaminergic neurodegeneration. The protective effect of TP-5 may involve the NF-κB/NLRP3 signaling pathway.

Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let-7 family microRNAs.

OBJECTIVE: Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high-fat and high-sugar (HFHS) diet. However, its effect and mechanism remain unclear. MATERIALS AND METHODS: RNA-Seq was used to detect the differentially expressed genes among each group. HFHS-induced POF mouse model was generated and injected with siRNA using Poly (lactic-co-glycolic acid) (PLGA) as a carrier. RESULTS: RNA-Seq suggested that 5TP promoted the expression of Yin Yang 2 (YY2) in mouse ovarian granulosa cell (mOGC) of HFHS-POF mice. Luciferase reporter assay indicated that 5TP promoted the binding of YY2 to the specific sequence C(C/T)AT(G/C)(G/T) on the Lin28A promoter and promoted Lin28A transcription and expression. We continuously injected PLGA-cross-linked siRNA nanoparticles targeting YY2 into HFHS-POF mice (siYY2@PLGA), which significantly reduced the therapeutic effect of 5TP. siYY2@PLGA injection also significantly attenuated the upregulation of Lin28a expression in mOGCs induced by 5TP and enhanced the expression of let-7 family microRNAs, thereby inhibiting the proliferation and division of mOGCs. qPCR results showed that there was a significant difference in the expression levels of exosome-derived Yy2 mRNAs between POF patients and normal women, and that there was a specific correlation between the expression level of exosome-derived Yy2 and the peripheral concentrations of the blood hormones pregnenolone, progesterone and oestradiol. CONCLUSIONS: Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibits the activity of let-7 family microRNAs and alleviates the ageing of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice.

The effect of thymopentin add-on in hepatitis B e antigen positive chronic hepatitis B after virus suppression by peginterferon plus entecavir therapy.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) was positively correlated with serological hepatitis B surface antigen (HBsAg) levels in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients. We evaluated whether Thymopentin (TP5) and interferon (IFN-a) had a synergic effect on HBV cccDNA and the effect of TP5 addition therapy on HBsAg clearance in CHB patients. Real-time PCR experiments were performed to test cccDNA in HepG2.2.15 cells. 45 HBeAg-positive CHB patients had been distributed into two groups randomly. Treatment group: 23 patients were treated with a 24-week TP5 on the basis of the treatment entecavir (ETV) and peginterferon alfa-2a (PegIFN alpha-2a). Control group: 22 patients were treated with ETV and PegIFNa-2a. The study period was 72 weeks. In HepG2.2.15 cells, TP5 5ug/ml and 10ug/ml respectively combined with IFN-a 2ku/ml could potently inhibit cccDNA level at 72 hours (P<0.05). In clinical study, mean HBsAg levels in two groups are not significantly different at different time points (p=0.112). However, changes of mean HBsAg levels in TP5 add-on group at different time points are significantly different (p<0.05). Patients with HBsAg levels <1500IU/ml in control group had higher HBsAg levels compared with patients with HBsAg levels <1500IU/ml in TP5 add-on group (P=0.019). The latter had the most pronounced HBsAg reduction. TP5 and IFN had a synergic effect on inhibiting cccDNA levels in HepG2.2.15 cells; Patients in treatment group showed no extra side effects compared with the control group. 24 weeks TP5 add-on treatment was safe and had a tendency to accelerate the decline of HBsAg when HBV-DNA was undetectable.

Myristic acid-modified thymopentin for enhanced plasma stability and immune-modulating activity.

Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of this study was to prolong the half-life and immune-modulating effects of thymopentin (TP5) by using the albumin binding strategy. We synthesized myristic acid-modified TP5 (TP5-MA) by conjugating a myristic acid-acylated lysine to a permissive site of TP5, which improved the albumin binding affinity of TP5-MA and dramatically enhanced its stability in human plasma. We observed well-preserved bioactivities of TP5-MA in RAW264.7 macrophages using a tumor necrosis factor (TNF)-α stimulation assay. Moreover, the prolonged immune-modulating effect of TP5-MA was confirmed by the normalized CD4+/CD8+ ratio in immune-depressed rat models, which resulted in a reduced administration frequency (twice per week). In general, the enhanced pharmacokinetic and pharmacodynamic properties of TP5-MA make it a promising product for the treatment of immunodeficiency diseases.

Thymopentin improves cardiac function in older patients with chronic heart failure.

OBJECTIVE: Recent studies have shown that activation of the immune system, inflammatory cell infiltration, and activation of inflammatory mediators play an important role in the development of heart failure. The purpose of this study was to investigate whether cardiac function can be improved by regulating the balance of lymphocyte subsets and cytokines. METHODS: Ninety-six patients with chronic heart failure (CHF) who were older than 60 years were randomly divided into two groups: CHF testing group (CHFT) received regular therapy and thymopentin (2 mg thymopentin per day, 15th as a course, three courses in total). CHF control group (CHFC) received regular therapy. Forty-five healthy individuals older than 60 years were used as normal controls. The ejection fraction of left ventricle (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), plasma high sensitive C-reactive protein (hsCRP), plasma brain natriuretic peptide (BNP), 6-min walking distance (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) assessment, lymphocyte subsets, and inflammatory cytokines were tested. RESULTS: The levels of LVEF, 6MWT, CD 3+, CD4+T cells, natural killer cells, CD4+/CD8+ and IL-10 in CHFT were increased (p<0.01) compared with CHFC, while BNP, hsCRP, MLHFQ, CD8+, TNF-α, IL-1ß, and TNF-α/IL-10 ratio in CHFT were decreased (p<0.01). LVEDD and LVESD were decreased, even though there was no significant difference between the two CHF groups. CONCLUSION: These data suggest that immune modulation therapy improve cardiac function and regulate cytokines and lymphocyte subsets in older patients with CHF.

A 6-year treatment experience for pemphigus: retrospective study of 69 Chinese patients.

There is a lack of data on treatment and prognosis of pemphigus in China. The aim of this study was to evaluate long-term follow-up and prognosis of pemphigus. Forty-seven inpatients with pemphigus vulgaris (PV) and 22 with pemphigus foliaceus (PF) were recruited in this retrospective study. The average age at onset was 51.6 and 54.9 years in PV and PF, respectively. High-dose systemic steroids were administered in 47 PV and 21 PF, of which 18 PV and 8 PF with adjuvant therapies. CD4 lymphocytopenia was found in 5 PV and 2 PF patients at admission and successfully treated by intravenous thymopentin daily. During a mean follow-up of 37.1 months, 41 PV and 19 PF reached remission, 30 PV and 9 PF relapsed, 4 PV and 2 PF died. Major causes of death were relapse of pemphigus due to discontinuation of oral steroids by the patients themselves (four cases) and severe infections (two cases, one with severe CD4 lymphocytopenia). The 1-year mortality rate of PV and PF was 8.5% and 4.5%, respectively. Cox regression analysis indicated that age at onset of pemphigus was an independent risk factor related to the elevated mortality. Our report confirmed the high mortality rate of pemphigus in a Chinese population and stressed that patient education was urgently needed to prevent relapses and deaths.

Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial.

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum ß2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.

Thymic peptides for treatment of cancer patients.

BACKGROUND: Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy. OBJECTIVES: To evaluate the effectiveness of pTE and sTP for the management of cancer. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010). SELECTION CRITERIA: Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis. MAIN RESULTS: We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10  for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23,  P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias. AUTHORS' CONCLUSIONS: Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles.

PURPOSE: Microparticles containing solid lipid nanoparticles (SLNs) are receiving increased attention as carriers for the lung delivery of the SLNs. Thus, we aim to prepare the hybrid microparticles and thoroughly evaluate their feasibility for the pulmonary drug delivery. METHODS: The microparticles were prepared by co-spray-drying the thymopentin (TP5)-loaded SLNs with bulking agents. Thereafter, we systematically estimated the potential of the microparticles as the carriers for the pulmonary delivery of the SLNs, including the investigations of their characteristics, aerodynamic properties, pharmacokinetics and pharmacodynamics. RESULTS: The spherical and hollow microparticles presented a size of 4.1 +/- 0.1 microm and a low tap density of 0.175 +/- 0.02 g/cm(3). In addition, the microparticles showed a high aerosolization efficiency (emitted dose of 98.0% +/- 1.23% and respirable fraction of 51.07% +/- 1.21%). Furthermore, the SLNs could be easily recovered from the microparticles without essential changes on their characteristics and the drug release behavior. The pharmacokinetic and pharmacodynamic studies suggested that, compared to i.v. TP5 solution, the bioavailability and therapeutic efficacy of TP5 were remarkably strengthened after the pulmonary administration of the microparticles. CONCLUSIONS: Taken together, we believe the microparticles were suitable for inhalation and possessed an ample potential for the pulmonary delivery of the SLNs.

[Mediation of cellular immune response by TP5 in pathogenesis of myasthenia gravis].

OBJECTIVE: To evaluate the effects of TP5 upon the production of IFN-gamma and different T cell subsets by human peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to provide experimental rationales for TP5 in clinical therapy of MG. METHODS: PBMCs were isolated from peripheral blood of MG individuals and cultured with anti-CD3. The level of IFN-gamma in culture supernatants was examined by ELISA. The subsets and frequency of IFN-gamma-producing cells were examined at a single-cell level by flow cytometry. RESULTS: After PBMCs stimulation with anti-CD3 and TP5 (300 microg/ml), the level of IFN-gamma expression was significantly inhibited (P(child) = 0.0001, P(adult) = 0.01); and the level of IFN-gamma expression from normal adult and child controls was also significantly inhibited (P(child) = 0.009, P(adult) = 0.0001). In addition, the inhibition of TP5 on the production of IFN-gamma by PBMCs from MG children was lower compared with normal child control. But as compared with normal adult control, the inhibition of TP5 showed no significant difference in MG adults (P(adult) = 0.481). TP5 inhibited the expression of IFN-gamma by CD8+ T cell and CD4+ T cell. CONCLUSION: TP5 can inhibit the response of cellular immune by decreasing the production of IFN-gamma in MG consequence display that the level of IFN-gamma significant decreased with the addition of TP5 and anti-CD3. But after considering the age, the level of IFN-gamma in MG children was no as much inhibited as normal child. TP5 inhibits the expression of IFN-gamma by CD8+ T and CD4+ T cells.

[Thymopentin 5 in treatment of relapse after extended thymectomy: a randomized comparative clinical trial of 135 patients with myasthenia gravis].

OBJECTIVE: To investigate the effect of thymopentin 5 (TP5) combined with immunosuppressive agents in treatment of relapse after extended thymectomy in patients with myasthenia gravis (MG). METHODS: One hundred thirty-five MG patients who were to undergo extended thymectomy, 62 adults and 73 children, were randomly assigned to 2 groups: non-TP5 group (n = 60) treated with intramuscular injection of prednisone + pyridostigmine daily for 3 months as a basic treatment, and TP5 group (n = 73), treated with prednisone + pyridostigmine + TP5 for 3 months. Follow-up was conducted for more than 1 year. RESULTS: The remission rates of children in the TP5 group at different time points were all markedly higher than those in the non-TP5 group, and the remission rates of children in the TP5 group during the period of 2 months to 2 years after thymectomy were all significantly higher (all P < 0.05). And the remission rates of the adults of the TP5 group during the period of 6 months to 2 years after thymectomy were all significantly higher than those of the non-TP5 group (all P < 0.05). In the pediatric cases the withdrawal rate of the TP5 group was significantly higher, and the relapse rate was significantly lower than those of the non-TP5 group. No side effect developed during the follow-up. CONCLUSION: TP5 is effective in reducing relapse and has a higher drug withdrawal rate, especially among children.

[Study on the efficacy and safety of high dose thymopentin combined with trans-artery chemoembolization for primary liver cancer].

OBJECTIVE: To evaluate the efficacy and safety of high doses of thymopentin (10 mg/d) combined with transartery chemoembolization for primary liver cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Withdrawal symptoms of ethanol are ameliorated by thymopentin in mice].

OBJECTIVE: To explore the effect of thymopentin (TP5) on the choice of ethanol and ameliorating withdrawal symptoms (anxiety) of ethanol in mice. METHODS: Mice were administered ethanol (v/v) in schedular fashion: 5% (1 week), 10% (1 week) and 15% (4 weeks), followed with the free choice between ethanol and water. Ethanol/(ethanol+water)x100% [E/(E+W)x100%] was measured as an index of ethanol selection. Light-dark box test and elevated plus maze test were chosen for the assessment of anxiety pre-drug and post-drug. After TP5 [0.2 mg/(kgxd), 0.4 mg/(kgxd)], i.p. or saline (vehicle control), i.p. for 14 days, the procedure was repeated. RESULT: (1) E/(E+W)x100%: the post-drug values of TP5 (0.2 mg/kg, 0.4 mg/kg) were lower significantly than the pre-drug values. (2) Light-dark box test: the post-drug values of number of entries and time spent in the light chamber of TP5 (0.2 mg/kg, 0.4 mg/kg) were more than the pre-drug values themselves and the post-drug value of saline. (3) Elevated plus maze test: the post-drug values of time spent on open arms of TP5 (0.2 mg/kg, 0.4 mg/kg) were more than the pre-drug values themselves and the post-drug value of salineìand the post-drug values of time spent on close arms of TP5 were less than the pre-drug values. CONCLUSION: TP5 could decrease the uptake of ethanol and ameliorate anxious behavior associated with ethanol withdrawal in mice.

[Clinical trial to verify the value of the CD14(+) monocyte human leukocyte antigen DR as a marker in evaluating immunosuppression in patients with severe sepsis].

OBJECTIVE: To verify that CD14(+) monocyte human leukocyte antigen DR (HLA-DR) may serve as a reliable index for immunosupression, and for prediction of prognosis as well as to evaluate the efficacy of Thymopentin (TP-5) to enhance immunologic function in patients with severe sepsis, and to evaluate the validity of compensatory anti-inflammatory response syndrome (CARS). METHODS: Patients in a SICU with symptoms and signs of severe sepsis conforming to the criteria set forth by ACCP/SCCM were enrolled in this clinical trial. CD14(+) monocyte HLA-DR was determined by flow cytometry. To those with HLA-DR<30%, TP-5, 1 mg, q.d. was administered till HLA-DR raised or death occurred. Before the treatment was begun and ended, CD14(+) monocyte HLA-DR(+) and cytokines[tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, IL-13] were respectively measured. RESULTS: Totally, 20 patients were enrolled in this study. Among them 15 survived and 5 died. After treatment with TP-5, CD14(+) monocyte HLA-DR was elevated in almost all the patients, including the nonsurvivors. However, only a statistically significant difference between the initial values and the final values was noted in the survivors. The levels of TNF-alpha and IL-6 dropped significantly concomitantly with the elevation of the CD14(+) monocyte HLA-DR in survivors. On the contrary, in the patients who died there was a tendency of an elevation of levels of these cytokines. No significant difference was found between the initial and final levels of both IL-10 and IL-13 with the treatment. CONCLUSION: 1. It was reconfirmed that the CD14(+) monocyte HLA-DR could be a reliable and valuable index to judge immunosupression in septic patients and determine the effectiveness of immunostimulative therapy. 2. It was reconfirmed that the level of CD14(+) monocyte HLA-DR can serve as an index to predict the outcome of septic patients. 3. TP-5, as a new immunostimulative agent used in sepsis, might be effective to revert immunosupression. However, a further clinical trial with a larger number of patients and a better control should be done to finally verify it. 4. It is found that immunosupression do not seem to be related with the balance between pro- and anti-inflammatory cytokines, suggesting that the hypothesis of CARS should be further appraised.

Phototherapy and systemic treatments.

A proportion of children and adults with moderate to severe atopic eczema are not adequately controlled with emollients and topical steroids, resulting in significant morbidity and disability. Studies indicate a significant placebo response, so randomized controlled trials of new treatments are vital. This article reviews the evidence for phototherapy and systemic treatments in atopic eczema.

[Therapeutic effects of Lamivudine in combination with Thymopentin on chronic hepatitis B].

OBJECTIVE: To explore the efficacy of anti-viral drug in combination with immunoregulatory agent in treatment of chronic hepatitis B. METHODS: 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. RESULTS: 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. CONCLUSIONS: Lamivudine in combination with thymopentin can exert great and lasting effects on HBV and is effective in normalization of ALT.

Successful interferon alpha therapy in atopic dermatitis of Besnier's prurigo pattern with normal serum IgE and blood eosinophil fraction: randomized case-controlled study.

A randomized case-controlled study was carried out to investigate for interferon alpha therapy in atopic dermatitis (AD) of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. Interferon alpha therapy was conducted on 14 non-responders to interferon gamma and subsequent thymopentin therapy among 100 atopic dermatitis patients. Eight patients who improved significantly, showed skin lesions of the Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. For the randomized prospective case-controlled study, 44 patients with the above characteristics were selected. Thirteen Besnier's prurigo patients were treated with interferon alpha therapy, ten with interferon gamma, ten with thymopentin, and the remaining 11 were untreated as the control group. With interferon alpha therapy, 11 out of 13 Besnier's prurigo patients with normal IgE and normal blood eosinophil fraction improved significantly, two out of ten improved with interferon gamma therapy, and none improved with thymopentin therapy or in the untreated control group. Interferon alpha therapy was effective on AD of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. These results suggest the possibility of non-IgE-mediated AD and the heterogeneity of atopic dermatitis.

Immunomodulatory agents for prophylaxis and therapy of infections.

The advent of the antibiotic era ushered in a shift towards non-pathogen-specific therapy of infectious diseases. This led to an overt emphasis on targeting microbial pathogens while strategies directed towards enhancing host immunity were neglected. In an effort to decrease sole reliance on antimicrobials, the time has come for a critical reappraisal of nonantibiotic, albeit immune response-enhancing substances. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this review succinctly demonstrate the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various microbial infections.

Review of thymic hormones in cancer diagnosis and treatment.

The thymus is an endocrine organ. A unified, physiological concept of humoral regulations of the immune response has emerged in the last three decades. The thymus is the major site of production of immunocompetent T lymphocytes from their hematopoietic stem cells. This complex process required direct cell to cell, receptor based interactions, as well as in situ paracrine information via the numerous cytokines and thymic hormones produced by the cells of thymic microenvironment. Thymic hormones induce in situ T-cell marker differentiation, expression and functions. These polypeptide hormones have also been shown by means of immunocytochemistry to localize in the reticulo-epithelial (RE) cells of the thymic cellular microenvironment. Due to the great complexity of the intrathymic maturation sequence of T lymphocytes and the diverse immunophenotypically unique subpopulations of T lymphocytes, it is quite unlikely that a single thymic humoral factor could control all of the molecular steps and cell populations involved. It is much more likely that an extremely rich and diverse, but genetically determined, milieu is present within the thymus, and that thus the control of intrathymic T lymphocyte maturation and the functional maturation of T cells involves the orchestral interaction of various thymic-specific factors and other molecules during the differentiation process. Thymosin fraction 5 and its constituent peptides influence several properties of lymphocytes including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, as well as the expression of various cell surface maturation/differentiation markers. Recently, derivatives of thymic hormones, mostly of thymosins, have been detected as products of neoplastically transformed cells and employed in the early diagnosis of neoplasms. In clinical trials, thymic hormones strengthen the effects of immunomodulators in immunodeficiencies, autoimmune diseases, and neoplastic malignancies. Combined chemo-immunotherapeutical anti-cancer treatment seems to be more efficacious than chemotherapy alone, and the significant hematopoietic toxicity associated with most chemotherapeutical clinical trials can be reduced significantly by the addition of immunotherapy.