thymalfasin and Inflammation

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Cannabinoids; COVID-19; COVID-19 Drug Treatment; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Eicosanoids; Humans; Inflammation; Protein Kinase Inhibitors; Roscovitine; Signal Transduction; Thymalfasin

Cystic fibrosis (CF) is a multisystem illness caused by abnormalities in the CF transmembrane conductance regulator (CFTR) gene and protein. CFTR is an ion channel regulating transport of chloride, bicarbonate, and water, and influencing sodium resorption. It is inherited as an autosomal recessive disorder, and with about 70,000 CF patients worldwide, it is the most common life shortening disease among persons of European descent. CFTR disease-causing mutations have been organized into six classes. :. Recently, small molecule targeted therapy for specific classes of CFTR abnormalities have included CFTR correctors that decrease protein degradation and CFTR potentiators that increase channel open probability enhancing chloride transport.. Although there are many novel medications in preclinical and clinical testing, there is need for safe and effective CFTR modulating drugs and immunomodulatory medications to decrease the abundant neutrophilic inflammation response in the airway without unwanted adverse effects. Thymosin alpha 1 treatment of airway cells isolated from phe508del CF patients and from CF knockout mice, decreased inflammation, increased CFTR maturation, and facilitated translocation of CFTR protein to the plasma membrane increasing channel activity. If similar results are seen in humans with CF, thymosin alpha 1 has the unique potential to be a single molecule therapy for treating CF airway disease.

Topics: Animals; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Discovery; Health Services Needs and Demand; Humans; Inflammation; Mice; Mice, Knockout; Mutation; Thymalfasin

Thymosin alpha 1 (Tα1) is a naturally occurring polypeptide of 28 amino acids, whose mechanism of action is thought to be related to its ability to signal through innate immune receptors. Tα1 (ZADAXIN®) is used worldwide for treating viral infections, immunodeficiencies, and malignancies. Owing to its ability to activate the tolerogenic pathway of tryptophan catabolism - via the immunoregulatory enzyme indoleamine 2,3-dioxygenase - Tα1 potentiates immune tolerance mechanisms, breaking the vicious circle that perpetuates chronic inflammation in response to a variety of infectious noxae.. Tα1 has never been studied in Cystic fibrosis (CF) in which the hyperinflammatory state is associated with early and nonresolving activation of innate immunity, which impairs microbial clearance and promotes a self-sustaining condition of progressive lung damage. Optimal CF treatments should, indeed, not only rescue CF transmembrane conductance regulator protein localization and functionality but also alleviate the associated hyperinflammatory pathology. Because of the inherent complexity of the pathogenetic mechanisms, a multidrug approach is required.. By providing a multipronged attack against CF, i.e. restraining inflammation and correcting the basic defect, Tα1 favorably opposed CF symptomatology in preclinical relevant disease settings, thus suggesting its possible exploitation for 'real-life' clinical efficacy in CF. This could represent a major conceptual advance in the CF field, namely the proposal of a drug with the unique activity to correct CFTR defects through regulation of inflammation.

Topics: Animals; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Immune Tolerance; Immunity, Innate; Inflammation; Proteostasis; Signal Transduction; Thymalfasin

To assess the effects of urinary trypsin inhibitor (UTI) ulinastatin combined with thymosin alpha1 (Tα1) on sepsis.. The meta-analysis included 8 randomized controlled trials (N=1112 patients) on UTI-based therapy for sepsis published before July 10, 2016. Two investigators independently extracted data and assessed the quality of each study. The short-term mortality rate, duration of mechanical ventilator and vasopressor use, length of intensive care unit stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and differences in inflammatory cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α) were assessed using statistical software.. Treatment of UTI combined with Tα1 (UTI+Tα1) decreased the short-term mortality rate in septic patients by 36%, 35%, and 31% for 28, 60, 90 days, respectively. UTI+Tα1 decreased the duration of mechanical ventilation, APACHE II score, and levels of IL-6 and tumor necrosis factor α. Treatment of UTI+Tα1 did not reduce the duration of vasopressor use and length of intensive care unit stay, or increase IL-10 levels. Because of the high heterogeneity of the included trials, the results should be carefully assessed.. Treatment of UTI+Tα1 can suppress the production of proinflammatory cytokines, decrease the APACHE II score, shorten the duration of mechanical ventilation, and improve the 28-day survival rate.

Topics: Adult; China; Glycoproteins; Humans; India; Inflammation; Intensive Care Units; Interleukin-10; Interleukin-6; Length of Stay; Middle Aged; Randomized Controlled Trials as Topic; Research Design; Respiration, Artificial; Sepsis; Severity of Illness Index; Software; Survival Rate; Thymalfasin; Thymosin; Treatment Outcome; Tumor Necrosis Factor-alpha

Inflammatory diseases are characterized by severe immune imbalances, leading to excessive or inappropriate release of mediators, which, in turn, result in massive damage to organs and systems. Effective means to control inappropriate immune reactions are often life-critical needs. Available data on the role of thymus-derived hormones in inflammation show their great potential.. The review aims to systematize information for the last two decades on immune system regulation by thymic peptide hormones, with a primary focus on the role of these hormones in the systemic inflammatory response and inflammatory diseases. Anti-inflammatory potential of three thymic hormones - thymulin, thymosin-alpha, and thymopoietin - is discussed, reviewing recently published clinical and experimental studies.. Our analysis revealed the regulation of inflammatory processes via thymic hormones that could be prospective for therapeutic application. This regulation may be mediated through thymic hormone effects on peripheral immune cell activities and bidirectional coupling between thymic hormones and the hypothalamic-pituitary-adrenal axis.. In view of the role of thymic hormones in immune and neuroendocrine systems, they could be suitable as therapeutic agents for inflammation.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Endocrine System; Hormones; Humans; Inflammation; Mice; Stress, Physiological; Thymalfasin; Thymic Factor, Circulating; Thymopoietins; Thymosin; Thymus Hormones

The peripheral immune system can promote either immunity or tolerance when presented with new antigens. Current knowledge withholds that populations of suppressor or regulatory T cells (T(reg) cells) constitute a pivotal mechanism of immunological tolerance. The potential role of malfunctioning T(reg) cells in chronic inflammatory immune and auto-immune diseases is well-documented. Learning how to successfully manipulate T(reg) responses could result in more effective vaccines and immunomodulators. We have already shown that Thymosin alpha1 (Talpha1), a naturally occurring thymic peptide first described and characterized by Allan Goldstein in 1972, by modulating signals delivered through innate immune receptors on dendritic cells, affects adaptive immune responses via modulation of Th cell effector and regulatory functions. We will discuss recent molecular mechanisms underlying the ability of Talpha1 to activate or inhibit immune responses.

Topics: Animals; Dendritic Cells; Humans; Immune System Diseases; Immune Tolerance; Immunity; Immunologic Factors; Inflammation; Signal Transduction; T-Lymphocytes, Regulatory; Thymalfasin; Thymosin; Thymus Gland

Thymosin alpha-1 (Talpha1) is a molecule retaining pleiotropic effects toward several pathological conditions, especially acting as a modulator of immune response and inflammation. However, molecular mechanisms underlying the peculiar, wide-range activity of Talpha1 have not been completely elucidated. To get information on the mechanism of action of Talpha1 and to find new potential applications, we performed the analysis of the transcription profile of 8300 genes in human peripheral blood mononuclear cells in vitro treated with Talpha1. Together with a variety of genes already known to be modulated by Talpha1, our analysis revealed a remarkable number of genes not yet described before to be modulated by this thymic peptide, revealing a complex scenario that underlines the role of this peptide as a regulator of lymphocyte functions. Here, we report the list of the more representative modulated genes and discuss their implications on the modulation of the innate and adaptive responses. Our results open new perspectives on the use of Talpha1 for the treatment of diseases associated with immune-disregulation.

Topics: Humans; Inflammation; Leukocyte Count; Lymphocytes; Thymalfasin; Thymosin; Thymus Gland

Thymosin alpha1 (Talpha1), first described and characterized by Allan Goldstein in 1972, is used worldwide for the treatment of some immunodeficiencies, malignancies, and infections. Although Talpha1 has shown a variety of effects on cells and pathways of the immune system, its central role in modulating dendritic cell (DC) function has only recently been appreciated. As DCs have the ability to sense infection and tissue stress and to translate collectively this information into an appropriate immune response, an action on DCs would predict a central role for Talpha1 in inducing different forms of immunity and tolerance. Recent results have shown that Talpha1: (a) primed DCs for antifungal Th1 resistance through Toll-like receptor (TLR)/MyD88-dependent signaling and this translated in vivo in protection against aspergillosis; (b) activated plasmacytoid DCs (pDC) via the TLR9/MyD88-dependent viral recognition, thus leading to the activation of interferon regulatory factor 7 and the promotion of the IFN-alpha/IFN-gamma-dependent effector pathway, which resulted in vivo in protection against primary murine cytomegalovirus infection; (c) induced indoleamine 2,3-dioxygenase activity in DCs, thus affecting tolerization toward self as well as microbial non-self-antigens, and this resulted in vivo in transplantation tolerance and protection from inflammatory allergy. Talpha1 is produced in vivo by cleavage of prothymosin alpha in diverse mammalian tissues. Our data qualify Talpha1 as an endogenous regulator of immune homeostasis and suggest that instructive immunotherapy with Talpha1, via DCs and tryptophan catabolism, could be at work to control inflammation, immunity, and tolerance in a variety of clinical settings.

Topics: Acquired Immunodeficiency Syndrome; Animals; Aspergillosis; Dendritic Cells; HIV Infections; Homeostasis; Humans; Hypersensitivity; Immunity, Innate; Inflammation; Mycoses; Neoplasms; Signal Transduction; Th1 Cells; Thymalfasin; Thymosin; Thymus Gland

To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification (CBP), thymosin alpha1, and combined therapy of CBP and thymosin alpha(1).. 91 Patients with severe sepsis aged > 18, with Marshall score>5. were randomly divided into 4 groups: CBP Group (n = 22) undergoing continuous renal replacement therapy (CRRT) or molecular adsorbents recirculating system (MARS) therapy once a day for 3 days in addition to classical Surviving Sepsis Campaign (SSC) therapy, Thymosin alpha(1) Group (n = 23) undergoing subcutaneous injection of thymosin alpha(1) 1.6 mg once a day for 7 days in addition to SSC therapy, Combined Therapy Group (n = 22) undergoing CBP combined with thymosin alpha(1) treatment in addition to SSC therapy, and SSC Group (treatment control group, n = 24) undergoing SSC therapy only. Peripheral blood samples were collected before treatment, and 3 and 7 days after the beginning of treatment (days 4 and 8) to detect the serum interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. The levels of CD(14)(+) monocyte human leucocyte antigen (HLA)-DR and T lymphocytes were monitored. The mechanical ventilation time, ICU stay length, and mortality within 28 d and mortality within 90 d were observed. Ten healthy persons were used as healthy control group.. Thirty-four of the 91 patients died within 28 d with a mortality of 77.4% (Death Group) and other 57 patients were put in Survival Group. The levels of serum IL-6, IL-10, and TNFalpha, and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher, and the HLA-DR level, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls (P < 0.05 or < 0.01). The levels of serum IL-6, IL-6/IL-10, TNFalpha, HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group (P < 0.05 or < 0.01). The CD(3)(+) T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group (all P < 0.05). The serum IL-6 and TNFalpha and IL-6/IL-10 were decreased, and HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) were increased significantly on day 8 in CBP and Combined Therapy Groups. The level of TNFalpha decreased, and the numbers of CD(3)(+) and CD(4)(+) T lymphocytes increased significantly on day 4 in Combined Therapy Group (P < 0.05 or P < 0.01). Compared with Thymosin Group, almost all the indexes of CBP and Combined Therapy Groups were improved, only the CD(3)(+) T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group (both P < 0.05). Compared with those of SSC Group, the mechanical ventilation time, length of ICU stay within 28 days, and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased, and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group (both P < 0.05).. Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis. Thymosin alpha(1) increases the cellular immunity, and CBP bi-modulates the immune turbulence, reduces the inflammatory mediators, and ameliorates the immune homeostasis. These 2 therapies also improve the clinical prognosis and the combination of both would be more effective.

Topics: Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Female; Hemofiltration; Humans; Immunity, Cellular; Inflammation; Male; Middle Aged; Prognosis; Prospective Studies; Sepsis; Thymalfasin; Thymosin

Topics: COVID-19; Cytokines; Humans; Inflammation; Leukocytes, Mononuclear; SARS-CoV-2; Thymalfasin; Thymosin

In the 1990's the macrophage-T-cell-theory of depression was posed stating that low grade inflammation and an abnormal T cell system destabilize the development and function of the emotional brain in such a way, that individuals become ultrasensitive to stress. Recently we gathered evidence that indeed higher frequencies of CD4+ memory T cells, lower frequencies of naive CD4 + T cells, higher frequencies of CD8 + T cells (the latter two in part elicited by Cytomegalovirus, CMV, infection) are a characteristic of Major Depressive Disorder (MDD). In MDD patients with a history of childhood trauma and severe depression monocytes are inflammatory activated. Low grade inflammation and T cell system defects have also been reported in patients with Common Variable Immune Deficiency (CVID) (next to antibody production defects). CVID patients show a higher prevalence of mild depression. The aim of this study was to determine T cell frequencies and monocyte inflammatory activation in CVID patients with and without depression. This study confirms that CVID patients have CMV independent decreases in the frequency of naïve CD4 + T cells and it de novo shows a CMV dependent increase in the expression of inflammatory genes in monocytes. CVID patients with depression are additionally characterized by a CMV independent increase in the frequency of naïve CD8 + T cells, while lacking monocyte inflammatory activation. In conclusion, depressed CVID patients have T cell abnormalities comparable to that of patients with regular MDD. These abnormalities are presently targeted by thymosin α1 in an open-label proof of concept trial.

Topics: CD8-Positive T-Lymphocytes; Common Variable Immunodeficiency; Cytomegalovirus Infections; Depressive Disorder, Major; Humans; Inflammation; Thymalfasin

Advanced or metastatic prostate cancer (PCa) is still an incurable malignancy with high lethality and a poor prognosis. Despite the remarkable success of immunotherapy against many types of cancer, most patients with PCa receive minimal benefit from current immunotherapeutic strategies, because PCa is an immune cold tumor with scarce T-cell infiltration in the tumor microenvironment. The aim of this study was to develop an effective immunotherapeutic approach for immune cold PCa tumors.. The therapeutic efficacy of androgen deprivation therapy (ADT) and zoledronic acid (ZA) plus thymosin α1 (Tα1) therapy was analyzed retrospectively in patients with advanced or metastatic PCa. The effects and mechanisms by which ZA and Tα1 regulated the immune functions of PCa cells and immune cells were evaluated by a PCa allograft mouse model, flow cytometric analysis, immunohistochemical and immunofluorescence staining assays, and PCR, ELISA, and Western blot analyses.. These findings uncover a previously undefined role for ZA and Tα1 in inhibiting the disease progression of immune cold PCa tumors by enhancing antitumor immunity and pave the way for the application of ZA plus Tα1 therapy as an immunotherapeutic strategy for treating patients with immunologically unresponsive PCa.

Topics: Androgen Antagonists; Androgens; Animals; CD8-Positive T-Lymphocytes; Humans; Inflammation; Male; Mice; Prostatic Neoplasms; Retrospective Studies; T-Lymphocytes, Cytotoxic; Thymalfasin; Tumor Microenvironment; Zoledronic Acid

This study aimed to research the clinical effect of Xuebijing combined with thymosin α1 on patients with severe pneumonia complicated with sepsis, and its effect on serum inflammatory factors. For this purpose, 81 cases of severe pneumonia complicated with sepsis were collected. All patients were given early treatments. 41 cases who received Xuebijing injection by intravenous drip were selected as the control group. 40 cases who were treated through subcutaneous injection of thymosin α1 based on Xuebijing injection by intravenous drip were selected as the study group. The body temperature, respiration, heart rate, leukocytes, other general conditions, blood gas indexes, serum IL-6, TNF-α and CRP levels, bacterial clearance rate and therapy effect were recorded and compared before and after treatment. Results showed that after treatment, the body temperature, respiration, heart rate, leukocytes and other general conditions of the study group were lower than those in the control group (all p<0.05). The blood gas indexes pH and PaCO2 levels of the study group were lower than those of the control group. The levels of serum interleukin-6 (IL-6), serum tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) in the study group were lower than those in the control group (all p<0.05). The bacterial clearance rate of the study group was lower than that of the control group (all p<0.05). The total effective rate of treatment of patients in the study group was higher than that of patients in the control group (all p<0.05). In general, Thymosin α1 and Xuebijing injection can improve the therapy effect of severe pneumonia complicated with sepsis, improve the hemorheology condition of patients, effectively remove bacteria and reduce the expression level of serum CRP, TNF-α, IL-6, IL-8 and other inflammatory factors in patients, which is worthy of clinical promotion.

Topics: Drugs, Chinese Herbal; Humans; Inflammation; Interleukin-6; Pneumonia; Sepsis; Thymalfasin; Tumor Necrosis Factor-alpha

The mechanism of inflammatory pain involves the central nervous system (CNS) and the immune system. It is reported that immunopotentiator thymosin alpha-1 (Tα1) can reduce inflammation, protect neurons and strengthen the immune function. However, the roles of Tα1 in inflammatory pain still remain unclear. In this study, we found Tα1 can attenuate the complete Freund's adjuvant (CFA)-induced mechanical allodynia and heat hyperalgesia. Meanwhile, it reduced the upregulation of CFA-induced inflammatory mediators (interferon (IFN)-γ, tumor necrosis factor-α and brain-derived neurotrophic factor). In addition, we found the Wnt3a/β-catenin pathway was activated in spinal cord after the injection of CFA, paralleling with pain hypersensitivity. However, Tα1 reversed this status. In summary, Tα1 could attenuate inflammatory pain by modulating the Wnt3a/β-catenin pathway. It might be related to the downregulation of inflammatory mediators.

Topics: Animals; beta Catenin; Chronic Pain; Hyperalgesia; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuralgia; Signal Transduction; Spinal Cord; Thymalfasin; Wnt3A Protein

Topics: Animals; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Cathelicidins; Cytokines; Drug Design; Drug Development; Humans; Inflammation; Intestinal Diseases; Male; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; NF-kappa B; Peptides; RAW 264.7 Cells; Thymalfasin; Tight Junctions

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems. The immunopotentiator thymosin alpha-1 (Tα1) has recently been reported to have anti-inflammatory and neuroprotective functions in rodents. However, how Tα1 affects inflammatory pain remains unclear. In the present study, intraperitoneal injection of Tα1 attenuated complete Freund's adjuvant (CFA)-induced pain hypersensitivity, and decreased the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in inflamed skin and the spinal cord. We found that CFA-induced peripheral inflammation evoked strong microglial activation, but the effect was reversed by Tα1. Notably, Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter (VGLUT) and down-regulated the vesicular γ-aminobutyric acid transporter (VGAT) in the spinal cord. Taken together, these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microglia-induced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.

Topics: Amino Acid Transport System X-AG; Animals; Cytokines; Freund's Adjuvant; GABA Plasma Membrane Transport Proteins; Glial Fibrillary Acidic Protein; Hyperalgesia; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Microglia; Pain; Spinal Cord; Thymalfasin; Tumor Necrosis Factor-alpha

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy. To date, no individual drug with pleiotropic beneficial effects is available for CF. Here we report on the ability of thymosin alpha 1 (Tα1)-a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent-to rectify the multiple tissue defects in mice with CF as well as in cells from subjects with the p.Phe508del mutation. Tα1 displayed two combined properties that favorably opposed CF symptomatology: it reduced inflammation and increased CFTR maturation, stability and activity. By virtue of this two-pronged action, Tα1 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF.

Topics: Adjuvants, Immunologic; Animals; Autophagy; Blotting, Western; Cell Line; Chloride Channels; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Cytokines; Disease Models, Animal; Epithelial Cells; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Immunoprecipitation; Indoleamine-Pyrrole 2,3,-Dioxygenase; Inflammation; Mice; Mice, Inbred CFTR; Patch-Clamp Techniques; Protein Stability; RAW 264.7 Cells; Respiratory Mucosa; Thymalfasin; Thymosin; Ubiquitin Thiolesterase; Ubiquitination

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