Protective effects of RU 41740, a bacterial immunomodulator, against experimental infections: induction of cytokine and immunoglobulin release in mice after oral administration

RU 41740 (Biostim(TM)) is an immunomodulator extracted from Klebsiella pneu moniae (strain O1:K2). In humans, it is able to reduce the number and durat ion of infectious exacerbations of chronic bronchitis. Using a mouse model of experimental infection, we found that oral RU 41740 administration strongly protected against gram-negative infections by preve nting lethal septicemia, and, to a lesser extent, protected against the gra m-positive intracellular pathogen L. monocytogenes. Oral administration of RU 41740 leads to the mobilization of newly dividing T and B cells in the thoracic duct lymph, reflecting the ability of the dr ug, to induce an immune response in gut-associated lymphoid tissue. In cell s isolated from mesenteric lymph nodes and spleen, RU 41740 leads to prefer ential release of the proinflammatory cytokines interleukin (IL)-12 and/or interferon (IFN)-gamma, as well as IL-IO, a cytokine involved in inhibiting the synthesis of these latter cytokines. RU 41740 also increases the serum total immunoglobulin (Ig)M concentration and elicits IgM and IgG antibodie s against the drug. Infection of mice with Klebsiella pneumoniae has similar functional consequ ences. Pretreatment of infected mice with RU 41740 leads to a fall in the h igh levels of proinflammatory cytokines (which could be detrimental), and t o an increase in IgG antibodies (which are protective). (C) 1999 Internatio nal Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.