During tissue injury, as occurs during infection and trauma, release of actin to the systemic vasculature and later polymerization appears to play a role in the systemic tissue injury associated with these conditions (1,2). Thymosine beta and thymosine alpha are two proteins produced by the thymus which appear to be very active in prohibiting extracellular actin polymerization (3,4). Inhibition of this intravascular actin polymeriztion may be beneficial during infection and trauma. In patients with septic shock, levels of thymosine B4 are markedly decreased (Personal communication from Dr. Mirela Fagarasan). Mice challenged with a lethal dose of endotoxin are significantly protected either by pretreatment or treatment up to 4 hs after endotoxin, with either thymosine B4 or alpha (Personal communication from Dr. Mirela Fagarasan). The activity of thymosine Fx can augmented by an amidation procedure which increases the molecule's half life. The survival benefits associated with these preparations have been verified in a number of well controlled experiments using the mouse model. It is not clear however whether such preparations will improve outcome during severe bacterial infection, where a number of pathogenetic mechanisms might be at work. We have developed an antibiotic treated rat model of E. coli intrapulmonary sepsis which is associated with reproducible mortality. We plan to conduct a number of studies shortly to initially evaluate the protective effect of three different thymosine preparations (B4, alpha and amidated alpha) in our rat model of pneumonia. These studies would function as pilot studies. If any of these preparations appear beneficial, an additional study would be designed and proposed for full evaluation of the nature of the protective effects associated with the preparations.
