thymosin and Shock--Septic

To investigate the effects of thymosin-alpha1 on cell immunity function and outcome in the patients with septic shock.. Forty-two patients with septic shock in the department of intensive care unit (ICU) and acute physiology and chronic health evaluation II (APACHE II) scores between 15 and 25. Patients with tumor, organ transplantation, chronic end-stage diseases and those who had used immunity inhibitor in recent 3 months or hormones were excluded. The patients were randomized into two groups: thymosin group (n=21) and control group (n=21). Patients in thymosin group were treated with thymosin-alpha1 1.6 mg by subcutaneous injection twice daily for 1 week in addition to the administration of broad-spectrum antibiotics to all patients. The levels of T lymphocyte subtype and natural killer (NK) cell were determined on the day 1, 3 and 7. At the same time, temperature, ICU stay days and duration of artificial ventilation, 28-day mortality and the expenses of hospitalization were recorded.. In the thymosin group, the levels of CD3+, CD4+, NK cells and the ratio of CD4+/CD8+ were increased obviously (all P<0.01). The mean afebrile period, stay days in ICU, duration of mechanical ventilation and hospital expenses as well as 28-day mortality were decreased obviously compared with those of control group (all P<0.01).. Thymosin-alpha1 can improve cell immunity function in the patients with septic shock. The cell immunity function is one of the main factors in influencing the prognosis of septic shock.

Topics: Adjuvants, Immunologic; Adult; Aged; Female; Humans; Killer Cells, Natural; Male; Middle Aged; Prognosis; Shock, Septic; T-Lymphocyte Subsets; Thymalfasin; Thymosin

Topics: Actins; Adult; Aged; Bacterial Infections; Biomarkers; Emergency Service, Hospital; Female; Hospitalization; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Noncommunicable Diseases; Organ Dysfunction Scores; Prognosis; Risk Factors; Sepsis; Shock, Septic; Thymosin

To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls.. F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml).. F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

Topics: Actins; Adult; Aged; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; ROC Curve; Shock, Septic; Systemic Inflammatory Response Syndrome; Thymosin

Thymosin beta(4) (Tbeta(4)), a highly conserved peptide with immunomodulatory properties, is the major actin-sequestering peptide in mammalian cells. Recent studies have established that Tbeta(4) can accelerate wound healing in full thickness skin wounds and following burn injuries to the cornea. In the eye studies, the accelerated healing due to Tbeta(4) was accompanied by a significant reduction in polymorphonuclear leukocyte (PMN) infiltration and a several-fold decrease in interleukin-1beta (p< or =0.015) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF1alpha, p< or =0.05). Given the recognized role of proinflammatory cytokines in septic shock and of extracellular F- and G-actin in the pathophysiology of multiple organ dysfunction, we have investigated the role of Tbeta(4) in sepsis. We report that an LD(50) dose of LPS (24 mg/kg) in rats resulted in a significant reduction of Tbeta(4) levels in the blood. Furthermore, administration of 100 microg of Tbeta(4) immediately following and at 2 and 4 h after an LD(50) dose of LPS (60 mg/kg) in mice significantly reduced mortality rates (p< or =0.024) and lowered blood levels of a number of inflammatory cytokines, eicosanoids, and other molecules that are highly elevated following endotoxin administration. In studies in human subjects given low doses of endotoxin (4 ng/kg LPS) and in patients with septic shock, we have also observed significant decreases in blood levels of Tbeta(4). The rapid disappearance of Tbeta(4) in the blood following LPS administration or during septic shock suggests that Tbeta(4) may be involved in early events leading to activation of the inflammatory cascade and ultimately the clinical sequelae of sepsis. The results of this study indicate that Tbeta(4) may have utility in the clinic in the treatment of septic shock and in syndromes associated with actin toxicities.

Topics: Adjuvants, Immunologic; Animals; Cytokines; Down-Regulation; Humans; Injections, Intraperitoneal; Lethal Dose 50; Lipopolysaccharides; Male; Mice; Mice, Inbred Strains; Rats; Rats, Sprague-Dawley; Shock, Septic; Thymosin