thymalfasin and Chronic-Disease

The hepatitis C virus (HCV) is a global public health problem, with chronic infection leading to development of cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Treatment of HCV is suboptimal with overall response rates of slightly greater than 50% when patients are treated with pegylated interferon alfa and ribavirin. Thymosin alpha 1 (Talpha1; TA-1) is an immunomodulatory peptide with intrinsic activities that might improve treatment outcomes for HCV by incorporation of this agent in current treatment paradigms. An extensive body of literature supports a possible role for this agent in difficult to treat populations. However, clinical trials to date have failed to conclusively support the role of TA-1 in combination interferon-based therapies. Therefore, the promise of TA-1 adjunctive therapy for HCV remains, but the proof will require investment in large randomized clinical trials of appropriate patient populations.

Topics: Carcinoma, Hepatocellular; Chronic Disease; Clinical Trials as Topic; Hepacivirus; Humans; Interferons; Liver Cirrhosis; Liver Neoplasms; Neoplasms; Randomized Controlled Trials as Topic; Ribavirin; Thymalfasin; Thymosin; Treatment Outcome

Thymosin alpha 1 (Tα1) is a powerful modulator of immunity and inflammation. Despite years of studies, there are a few reports evaluating serum Tα1 in health and disease. We studied a cohort of healthy individuals in comparison with patients affected by chronic inflammatory autoimmune diseases. Sera from 120 blood donors (healthy controls, HC), 120 patients with psoriatic arthritis (PsA), 40 with rheumatoid arthritis (RA) and 40 with systemic lupus erythematosus (SLE), attending the Transfusion Medicine or the Rheumatology Clinic at the Policlinico Tor Vergata, Rome, Italy, were tested for Tα1 content by means of a commercial enzyme-linked immunosorbent assay (ELISA) kit. Data were analysed in relation to demographic and clinical characteristics of patients and controls. A gender difference was found in the HC group, where females had lower serum Tα1 levels than males (P < 0·0001). Patients had lower serum Tα1 levels than HC (P < 0·0001), the lowest were observed in PsA group (P < 0·0001 versus all the other groups). Among all patients, those who at the time of blood collection were taking disease-modifying anti-rheumatic drugs (DMARD) plus steroids had significantly higher Tα1 levels than those taking DMARD alone (P = 0·044) or no treatment (P < 0·0001), but not of those taking steroids alone (P = 0·280). However, whichever type of treatment was taken by the patients, serum Tα1 was still significantly lower than in HC and there was no treatment-related difference in PsA group. Further prospective studies are necessary to confirm and deepen these observations. They might improve our understanding on the regulatory role of Tα1 in health and disease and increase our knowledge of the pathogenesis of chronic inflammatory autoimmune diseases.

Topics: Adult; Aged; Autoimmune Diseases; Biomarkers; Case-Control Studies; Chronic Disease; Female; Humans; Inflammation; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Thymalfasin; Thymosin; Treatment Outcome; Young Adult

Chronic purulent rhinosinusitis (CPR) is an inflammatory condition of unknown origin. Although various medical and surgical treatment modalities are available, 5-10% of patients remain refractory. Immune deficiency is one of the underlying risk factors for this disease. Earlier studies demonstrated disturbances in cell-mediated immunity and defects in monocyte chemotaxis in CPR. Treatment with the thymic hormone preparation thymostimulin led to significant clinical improvement in patients and in vitro restoration of monocyte chemotaxis. Unfortunately, thymostimulin became unavailable, which has led to recent interest in the immunomodulatory effects of the thymic peptide thymosin α1, which has demonstrated some benefit for CPR. Our current in vitro work focuses on the potential effects of thymosin α1 on monocyte function and gene expression profiles in order to understand its effects and mechanisms of action. Future clinical studies will evaluate the potential significance of thymosin α1 in treatment of CPR patients.

Topics: Cells, Cultured; Chronic Disease; Humans; Immunity, Cellular; Immunologic Factors; Monocytes; Rhinitis; Sinusitis; Thymalfasin; Thymosin

Serum concentrations of thymosin alpha-1 (TA-1), an immunoregulatory peptide, were assayed in patients with chronic hepatitis B infection and volunteer blood donor controls. Coded samples were tested using a radioimmunoassay. The TA-1 concentrations in HBsAg-positive patients averaged 1555 pg/ml, whereas in the control group, the mean TA-1 in serum was 2159 pg/ml (P less than 0.001). Similar results were found for age- and sex-matched pairs. The TA-1 concentration was not associated with HBe antigen/antibody status or with values of liver-associated enzymes. Analysis of T-cell subsets in nine HBsAg carriers revealed significantly decreased CD4 (helper)-cells, both in absolute numbers and as the percentage of total lymphocytes present. These data suggest that individuals with chronic hepatitis B infection have a relative deficiency of the immunomodulatory peptide TA-1, which may contribute to the characteristics of the resultant T-cell population.

Topics: Adult; Alanine Transaminase; Carrier State; Chronic Disease; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Humans; Male; Middle Aged; Radioimmunoassay; T-Lymphocytes; Thymalfasin; Thymosin