Modulation of mature B cells in mice following treatment with ouabain.

Ouabain (OUA) is an endogenous hormone released by the adrenal gland under stress situations. Steroid hormones and glucocorticoids have been characterized as selective inhibitors of lymphopoiesis. The present report shows in vivo modulation of mature B cells in bone marrow, spleen and peripheral blood by ouabain. Mice injected intraperitonially (i.p.) with ouabain 0.56 mg/kg for 3 consecutive days displayed, 24 h after last injection, a decreased cellularity in the bone marrow with diminution of the mature B cell subpopulation while the other B cell subpopulations were preserved. Percentually, the myeloid lineage in bone marrow was increased by ouabain. Numbers of mature B lymphocytes in spleen and peripheral blood were reduced following in vivo treatment. In vitro, the B cell populations were not affected. The effects appear to be independent of steroid hormones and strain. The presence of stable levels of glucocorticoids seems to be important because the effects could only be observed from the fourth week animal's life, when glucocorticoid levels are stable. These results open new perspectives for a potential use of ouabain as an immunomodulator.

Inhibition of B cell development by kalanchosine dimalate.

Kalanchoe brasiliensis (Kb) is a medicinal plant from the Crassulaceae family, used in folk medicine to treat inflammatory and infectious diseases. Here we show that short-term treatment of mice with a highly purified compound named kalanchosine dimalate (KMC), obtained from Kb, led to a strong and selective inhibition of B cell development in the bone marrow, without affecting the myeloid lineage development. Numbers of mature B lymphocytes in bone marrow or peripheral lymphoid organs were preserved in KMC treated mice. The inhibitory effect of KMC was acute and rapidly reverted with the interruption of the treatment. In vitro, KMC, inhibited the interleukin-7 dependent proliferation of B cell precursors and do not induce cell death. Also in vitro, the maturation of B cell precursors was not affected by KMC. KMC does not inhibit the proliferative response to IL-3 or IL-2. These results suggest that KMC is selectively affecting B cell lymphopoiesis, possibly acting on the IL-7 signaling pathway, opening new perspectives for a potential therapeutic usage of Kb derived drugs.

Selective blockade of lymphopoiesis induced by kalanchosine dimalate: inhibition of IL-7-dependent proliferation.

Lymphopoiesis and myelopoiesis continuously generate mature cells from hematopoietic cell progenitors during the lifetime of the organism. The identification of new endogenous or exogenous substances that can act specifically on the differentiation of distinct cell lineages is of relevance and has potential therapeutical use. Kalanchoe brasiliensis (Kb) is a medicinal plant from the Crassulaceae family, used in folk medicine to treat inflammatory and infectious diseases. Here, we show that short-term treatment of naïve mice with Kb led to a strong and selective inhibition of lymphopoiesis, affecting B and T cell lineages without reduction of the myeloid lineage development. Similar effects were observed after treatment with the highly purified compound kalanchosine dimalate (KMC), obtained from Kb. Numbers of mature lymphocytes in secondary lymphoid organs were preserved in Kb(KMC)-treated mice. The effect of Kb(KMC) was not a result of secondary augmentation of plasma levels of endogenous corticoids; neither involves TNF-alpha, type-I IFN, or TLR2/TLR4 ligands, which have all been described as selective inhibitors of lymphopoiesis. Flow cytometry analysis of the phenotypes of T and B cell precursors indicate a blockade of maturation on IL-7-dependent, proliferative stages. In vitro, Kb(KMC) inhibited the IL-7-dependent proliferation of pre-B cells and does not induce massive apoptosis of B and T cell precursors. These results suggest that Kb(KMC) is selectively blocking lymphopoiesis through a mechanism that does not involve the previously characterized substances, possibly acting on the IL-7 signaling pathway, opening new perspectives for a potential therapeutic use of Kb-derived drugs.