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PubMed2006

Newer therapeutic approaches for systemic lupus erythematosus: immunosuppressive agents.

There has been unprecedented growth in new therapeutic approaches for the treatment of systemic lupus erythematosus (SLE). These approaches include re-evaluation of the doses and duration of therapy with traditional agents, including intravenous cyclophosphamide and azathioprine. Drugs that were developed for other uses are being applied to specific SLE manifestations, and have spurred larger scale trials for overall disease activity. In addition, several new agents show promise in clinical trials; many have safer toxicity profiles than do traditional therapies. Some of these agents have multiple immunomodulatory effects, whereas others interfere with a specific immunologic process in one of the pathogenetic pathways of SLE activity.

Calcineurin Inhibitors↗
PubMed1997

Unique action of an immunosuppressive agent, deoxyspergualin, on hematopoiesis in mice.

Deoxyspergualin (DSG) is an immunosuppresive agent of proven effectiveness in the prevention and treatment of transplant rejection; its most frequent side effect is reversible bone marrow suppression. To clarify the mechanisms of bone marrow suppression induced by DSG, we monitored the numbers of peripheral blood and marrow stem cells in C3H/HeN mice receiving 14 days of DSG injections at a highly immunosuppressive dose of 10 mg/kg/day. In the peripheral blood cells, DSG induced severe anemia and mild leukopenia because of a decrease in granulocyte counts, although these phenomena were reversible. During DSG administration, nucleated cell counts in the femur also markedly decreased, whereas the absolute numbers of various stem cells and progenitor cells, except for erythroid colony-forming units (CFU-E), remained normal or increased; CD34- or c-kit-positive and lineage-negative cell levels markedly increased on the day DSG administration ceased. These findings indicate that DSG-induced anemia and leukopenia are not initiated by a generalized killing of these stem cells, but rather by a transient suppression of their ability to mature. Significantly, the severe anemia induced by DSG resembles pure red cell aplasia in humans, because there were marked decreases in peripheral reticulocytes, marrow CFU-E, and erythroblasts, with no decrease in renal erythropoietin mRNA expression. Furthermore, DSG-induced anemia was completely ameliorated by treatment with human recombinant erythropoietin.

Animals↗
PubMed1989

Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2.

The mechanism whereby FK506 inhibits immune responses was assessed in in vitro human studies. FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA. Complete inhibition was obtained at the concentration of 0.25 nM of FK506 for IL-2 and 1 nM of FK506 for gamma-IFN production. Inhibition of 50% (IC50) was detected with 0.06 nM for IL-2 and 0.25 nM for gamma-IFN production. On the other hand, FK506 could not inhibit the B cell-stimulating factor 2 (BSF-2) production of PBMC, indicating the possibility that FK506 might spare the B cell function. Cloned T cells and cloned B cells, once activated, were scarcely affected by the agent; neither IL-2-driven proliferation of cloned T cells nor BSF-2-driven proliferation of cloned B cells was inhibited by FK506 at any concentration.

Adult↗
PubMed2001

[Biological effects of microorganisms, their substances and immunosuppressive agents in mice].

The author provide evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defence. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating affect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora. With ageing, effect of immunomodulants can change and become indifferent or even suppressive. Dose-dependence of stimulating or suppressing effect of immunomodulants may be related to their non-immunological effects (endotoxin effect, bacterial translocation). Finally, on the basis of the results, the authors consider the germfree mouse suitable for examining the effect of a given agent in the practice, on one hand, and for observing the host organism's reactions, free from the influence of the normal microbial flora, on the other. Along with the known physiological and pathological events, the results draw also attention to as distant fields as drug sensitivity, drug interactions influencing drug sensitivity. The author put emphasis on importance of germfree environment during immunosuppressive treatments in humans and when making special examinations under experimental conditions.

Aging↗