Stimulation of cell-mediated immunity by bestatin correlates with reduction of bacterial persistence in experimental chronic Salmonella typhimurium infection

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Abstract
The effect of bestatin, a low-molecular-weight immunomodulating drug isolated from Streptomyces olivoreticuli, on Salmonella typhimurium infection was elaborated. Bestatin enhanced the delayed-type hypersensitivity reaction against S. typhimurium in a dose- and time-dependent manner. Parallel to the activation of delayed-type hypersensitivity reaction, bestatin reduced the amount of persistent bacteria in livers and spleens as well as the amount of necrotic foci found in these organs. This was shown when bestatin was given either prophylactically or therapeutically. The therapeutic effect of bestatin was even seen when the drug was given in the chronic phase of the infection, i.e., 6 days after inoculation of the animals with the infectious agent. No influence of bestatin, however, could be observed on the initial multiplication rate of S. typhimurium and concomitantly on the initial mortality rate of the infected mice. As bestatin has no direct antibiotic effect on S. typhimurium, it must be concluded that the therapeutic effects of the drug on chronic infection must be solely contributed to elevation of the host's own defense mechanisms.