Effect of transforming growth factor beta on experimental Salmonella typhimurium infection in mice

We have investigated the effect of the in vivo administration of recombinan t transforming growth factor beta (rTGF-beta) on the pathogenic mechanisms involved in Salmonella typhimurium experimental infection in mice. The prot ective response elicited by macrophages was induced by rTGF-beta(1) by 2 da ys after experimental infection, as demonstrated by an increased NO product ion, while the humoral protective effect began with cytokine mRNA expressio n 2 days after the challenge and continued after 5 days with cytokine relea se and lymphocyte activation. We demonstrated that all mice who received rT GF-beta(1) survived 7 days after infection. The number of bacteria recovere d in the spleens and in the livers of rTGF-beta(1)-treated mice 2 and 5 day s after infection was significantly smaller than that found in the same org ans after phosphate-buffered saline (PBS) inoculation, Furthermore, 2 and 5 days after infection, splenic macrophages from rTGF-beta(1)-treated mice s howed a greater NO production than did those from PBS-treated mice. The eff ect of rTGF-beta(1) on S. typhimurium infection in mice was correlated with the expression of cell costimulatory CD28 molecules. Five days after S. ty phimurium infection, the percentage of CD28(+)-expressing T cells in spleni c lymphocytes from rTGF-beta(1)-treated mice increased with respect to that from control mice, Gamma interferon (IFN-gamma) mRNA was present in a grea ter amount in spleen cells from rTGF-beta(1)-treated mice after 2 days, alt hough the intensity of the band decreased 5 days after the challenge, A sim ilar pattern was obtained with the mRNAs for interleukin-1 alpha (IL-1 alph a), IL-6, TGF-beta, and inducible nitric oxide synthase, which showed great er expression in cells obtained from rTGF-beta(1)-treated and S. typhimuriu m-infected mice 2 days after challenge. The treatment with rTGF-beta(1) ind uced an increase in IL-1 alpha and IFN-gamma release in the supernatant of splenocyte cultures 5 days after the experimental infection with S. typhimu rium, Moreover, we demonstrated that 5 days after infection, the IFN-gamma titer was significantly greater in the sera of rTGF-beta-treated mice than in those of PBS-treated mice. Also, hsp60 showed greater expression 2 days after the challenge in splenocytes from rTGF-beta(1)-treated mice, The role played by proinflammatory and immunoregulatory cytokines and by CD28 is di scussed.