Although tacrolimus has been studied in a wide variety of experimental animal models, we are the first group to systematically study the effect of tacrolimus on rat renal allograft survival, as primary therapy and as anti-rejection therapy, in comparison with cyclosporin A (CyA). Renal grafts were transplanted from BN to LEW rats. Tacrolimus and CyA were administrated orally from day 0 for SO days as primary therapy after grafting.
Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.
Although tacrolimus has been studied in a wide variety of experimental animal models, we are the first group to systematically study the effect of tacrolimus on rat renal allograft survival, as primary therapy and as anti-rejection therapy, in comparison with cyclosporin A (CyA). Renal grafts were transplanted from BN to LEW rats. Tacrolimus and CyA were administrated orally from day 0 for SO days as primary therapy after grafting.
Abstract-The antiallergic activity of sodium 10-(2,3-dimethyl pentanamido)-4-oxo-4H-pyrimido [1,2-C] quinazoline-3-carboxylate•(hydrate(FR50948) was studied and compared with the activities of sodium cromoglycate (SCG) and lodoxamide.FR50948 had inhibitory effects on type I and type III allergic reac tions, but not on type II and IV allergic reactions.FR50948 also had weak inhi bitory effects on inflammation (carrageenin paw edema and adjuvant arthritis) and SRS release from rat neutrophils, but no antagonistic effects to histamine and serotonin.The inhibitory effect of FR50948 on IgE-mediated type I allergic reac tions was essentially the same as those of SCG and lodoxamide, because FR50948 inhibited the histamine release from rat peritoneal mast cells and had cross tachy phylaxis with SCG in the rat PCA test.However, FR50948, like lodoxamide, had a stronger activity than SCG and was effective by the oral route, unlike SCG which was effective only by the parenteral route.Furthemore, the inhibitory effects of FR50948 on type III reactions and inflammatory reactions were much more potent than those of SCG and equal to those of lodoxamide, and the effect on IgG-mediated PCA was stronger than that of either reference drug. These results suggest that FR50948 will be beneficial in clinical use.
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