In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.)

The regulation of the "spontaneously" occurring ("background") Ig synthesis of mice has been studied by determining the numbers of IgM-, IgG- and IgA-secreting cells and a part of the IgM antibody-specificity repertoire in spleen, bone marrow (BM) and mesenteric lymph nodes (MLN) of conventional and "antigen-free" mice. These antigen-free mice were germ-free raised and fed an ultrafiltered solution of chemically defined low molecular weight nutrients, and thus devoid of exogenous antigenic stimulation. The secretion of IgM, IgG and IgA by spleen, BM and MLN cells was assessed in the protein A plaque assay, while specific IgM antibody-secreting cells were detected by plaque assays specific for differently haptenated sheep red blood cells. In general, antigen-free and conventional mice were found to have roughly equal numbers of IgM-secreting cells in spleen and BM. The number of IgG-secreting cells in the spleen of antigen-free mice was the same as in the spleen of conventional mice, but in the BM their number was 3-5-fold decreased. About one half of the antigen-free mice did not have MLN, and in the half which did, 5 times less IgM- and more than 100-fold less IgG-secreting cells were found as compared with conventional mice. The number of IgA-secreting cells in antigen-free mice was drastically decreased in all three organs tested. The antibody-specificity repertoire of the "background" IgM-secreting cells in the spleen and BM of the antigen-free and conventional mice was much alike. This indicates that in antigen-free mice the available antibody repertoires are established independently of exogenous and/or mitogenic stimulation.

This study investigates the influence of exogenous antigenic stimulation on the serum immunoglobulin levels and the levels of circulating natural antibodies against carbohydrate antigens. Thus, BALB/c mice, raised in a germ-free environment and fed a chemically defined, ultrafiltered diet (GF-CD), were employed. These mice had normal serum IgM levels, but IgG and IgA levels were approximately 5% of conventionally reared littermates. The concentrations of all four IgG isotypes were equally low. The variable part of the heavy chains of naturally occurring BALB/c antibodies against a number of carbohydrate antigens, including 3-fucosyllactosamine (3-FL), levan and dextran, are encoded by VH441, and these antibodies express cross-reactive idiotopes recognized by the monoclonal antibodies 6C4 and 6B1. Antibodies against levan and dextran were lower in GF-CD than in conventional mice, but levels of anti-3FL antibodies, and 6C4 and 6B1 idiotopes, were comparable to those in conventional animals. Peptidoglycan polysaccharide complexes (PPC) are carbohydrate antigens of bacterial origin, like levan and galactan. Naturally occurring antibodies against PPC were found in the serum of conventional mice, but were severely reduced in GF-CD mice. The results indicate that most naturally occurring antibodies against carbohydrate antigens of bacterial origin found in conventional mice are caused by exogenous stimulation.

The pregnancy hormone human chorionic gonadotropin (hCG) has been suggested to play an immunoregulatory role in addition to its endocrine function, thus contributing to the prevention of fetal rejection. We hypothesized that hCG is involved in the maternal-fetal immune tolerance by the regulation of dendritic cell (DC) function. Therefore, we studied the effect of hCG on DC maturation. Upon hCG treatment in combination with LPS, mouse bone marrow-derived DC (BMDC) increased the ratio of IL-10:IL-12p70, down-regulated TNF-alpha, and decreased antigen-specific T cell proliferation. Addition of hCG together with LPS and IFN-gamma blocked MHC class II up-regulation, increased IL-10 production, and decreased the antigen-specific T cell proliferation by DC. Splenic DC showed similar results. Upon hCG treatment, IDO mRNA expression and its metabolite kynurenine were increased by LPS- and IFN-gamma-stimulated DC, suggesting its involvement in the decreased T cell proliferation. To study the effect of hCG on DC differentiation from precursors, BMDC were generated in the continuous presence of hCG. Under this condition, hCG decreased cytokine production and the induction of T cell proliferation. These data are suggestive for a contribution of hCG to the maternal-fetal tolerance during pregnancy by modifying DC toward a tolerogenic phenotype.