[Rich selenium-Banqiao-Codonopsis Pilosula mixture enhances immune function of aging mice].
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To investigate the effect of rich selenium-Banqiao-Codonopsis Pilosula (RSBCP) mixture on the immune functions of the aging mice.Sixty Kunming mice (half male and half female) were randomly divided into high-, middle- and low-dose RSBCP mixture groups, model group and control group, with twelve mice in each group. The control group was injected intraperitoneally with 500 mg/(kg.d) normal saline and the other groups were injected with the same amount of D-galactose. The RSBCP mixture high-, middle- and low-dose groups were respectively gavaged with 100, 50, 25 g/(kg.d) RSBCP mixture at the moment when D-galactose was injected. The model group and control group were given the same amount of distilled water instead. The mice were killed at the 30th days and the indexes of thymus and spleen were measured. The serum levels of IgG, IgM, C3, C4, interleukine 2 (IL-2), IL-6 and tumor necrosis factor alpha (TNF-α) were detected by ELISA and the major T-cell subsets of splenocytes were analyzed by flow cytometry.Compared with the control group, the indexes of thymus and spleen in the model group decreased obviously; the serum levels of IgG, IgM, C3, C4, IL-2 and IL-6 were reduced significantly and the level of TNF-α increased significantly. Compared with the model group, the indexes of thymus and spleen in the RSBCP mixture groups increased obviously; the levels of IgG, IgM, C3, C4, IL-2 and IL-6 were raised significantly and the level of TNF-α decreased significantly. Compared with the control group, the indexes of thymus and spleen in the RSBCP mixture high-dose group increased obviously; the levels of IgG, IgM, C3, C4, IL-2 and IL-6 were lifted significantly and the level of TNF-α decreased significantly. The indexes of thymus and spleen and the levels of IgG, IgM, C3, C4, IL-2 and IL-6 in the RSBCP mixture middle- and low-dose groups had no obvious differences from those of the control group. Compared with the control group, the model group showed significantly decreased numbers of CD3⁺ T, CD4⁺ T, CD44⁺ T cells and significantly increased number of CD8⁺ T cells. Compared with the model group, the RSBCP mixture groups showed significantly increased numbers of CD3⁺ T, CD4⁺ T, both the high- and middle-dose groups showed significantly increased numbers of CD44⁺ T cells and significantly decreased number of CD8⁺ T cells.RSBCP mixture could delay the atrophy of thymus and spleen in the aging mice, dramatically elevate serum levels of IgG, IgM, C3, C4, IL-2, IL-6, lower the level of TNF-α, and influence the proportions of T cell subsets. The mixture plays a role in enhancing the immune function of aging mice.Keywords:
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We studied the effects of tumor necrosis factor-alpha (TNF alpha), a macrophage-derived pleiotropic cytokine produced during the inflammatory/immune response, on the function of the hypothalamic-pituitary-adrenal (HPA) axis of the rat. Intravenous injections of TNF alpha stimulated plasma ACTH and corticosterone secretion in a dose-dependent fashion. This effect was inhibited by a rat CRH antiserum that was administered to the rats 1 h before the TNF alpha injections. This suggested that CRH is a major mediator of the HPA axis response to TNF alpha. We subsequently evaluated the ability of TNF alpha to influence CRH and ACTH secretion in vitro by explanted rat hypothalami in organ culture and by dispersed rat anterior pituicytes in primary culture respectively. Hypothalami were incubated for 40 min with graded concentrations of TNF alpha (10 pM to 1 microM). This cytokine stimulated CRH secretion in a dose-dependent fashion, with an EC50 of 6.7 x 10 pM (P less than 0.05). Preincubation of hypothalamic explants with dexamethasone, indomethacin (1 microM), eicosatetraynoic acid (10 microM), or nordihydroguaiaretic acid (30 microM) resulted in inhibition of TNF alpha-stimulated CRH secretion (P less than 0.05). Interestingly, 4-h incubation with TNF alpha had no effect on ACTH secretion from rat anterior pituicytes at a concentration of 10 nM. Higher concentrations of TNF alpha (100 nM and 1 microM), however, elicited a dose-dependent increase in the ACTH concentration in the medium. Our results suggest that TNF alpha represents one of the immune response mediators that directly or via stimulation of other cytokines act as activators of the HPA axis during immune/inflammatory reactions. This effect appears to be glucocorticoid suppressible and eicosanoid mediated. The primary site of action of TNF alpha appears to by the hypothalamic CRH-secreting neuron. Some pituitary and adrenal effects of TNF alpha, however, cannot be excluded.
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Experiments designed to assess the importance of age of donors and recipients in cellular transfer of experimental allergic encephalomyelitis (EAE) in inbred Lewis rats indicate: (a) that lymph node cells (LNC) of suckling rats sensitized to neuroantigen-adjuvant are just as effective in transfer of the disease to adult recipients as LNC from similarly sensitized adult donors, (b) that EAE can be transferred to suckling rats just as well as adults using lymphoid cells from either suckling or adult donors, and (c) while relatively low numbers of sensitized splenocytes from suckling or adult donors may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis rats.
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The effects of long-term corticotropin-releasing hormone (CRH) infusion in the lateral ventricle of the rat on hypothalamic-pituitary-adrenocortical (HPA) axis parameters and on the immune system function were studied. Compared with infusion of vehicle, the CRH treatment produced a sustained overactivity of the HPA axis, as evidenced by elevated plasma ACTH and corticosterone levels, increased anterior pituitary POMC messenger RNA (mRNA) expression, and adrenal enlargement. Long-term CRH treatment also inhibited body weight gain and reduced thymus and spleen weight. In the CRH-treated animals, both Concanavalin A (Con A)-induced T lymphocyte proliferation and lipopolysaccharide (LPS)-induced B lymphocyte mitogenesis was largely suppressed. Surprisingly, interleukin-2 (IL-2) levels were higher in supernatants of splenocyte cultures from CRH-treated rats than in those of control animals. However, IL-2 receptor alpha chain (IL-2R alpha) mRNA expression after Con A stimulation was highly suppressed in the CRH-treated animals. In addition, Northern blot analysis of RNA from splenocytes isolated from spleens of CRH-treated rats revealed a marked expression of IL-1 beta mRNA, in contrast to the barely detectable levels of this cytokine in control animals. Moreover, incubation of total splenocytes and spleen macrophages with LPS resulted in an enhanced induction of IL-1 beta mRNA in cells of CRH-treated rats compared with that of control animals. When adrenalectomized rats were treated with CRH or vehicle, the effects of the CRH treatment on T and B cell proliferation, IL-2 production, and IL-1 beta mRNA expression were abolished. Thus, a continuously increased HPA axis drive results in disparate changes in immune system function. Whether the observed changes in cytokine expression should be regarded as physiologically adaptive adjustments in support of immune function or as potentially pathological anomalies remains to be elucidated.
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Zinc-α2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese ( ob/ob ) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-α (TNFα) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese ( fa/fa ) Zucker rats. In contrast to Zag expression, Tnfα mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFα reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFα treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFα.
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Tumor necrosis factor-α (TNF; cachectin), a peptide secreted from stimulated macrophages, mediates some of the metabolic derangements in inflammatory and neoplastic disorders. To determine whether TNF is responsible for the changes in hypothalamic-pituitary-thyroid (HPT) function in nonthyroid illnesses, we administered synthetic human TNF to male Sprague-Dawley rats. The rats were given TNF or saline (control; both pair fed and nonpair fed) iv (six to eight per group). HPT function was tested 8 h after administration of 200 μg TNF/kg BW, 8 h after 5 days of 150 μg TNF/kg BW, and 8 h after a 3-day series of 50, 200, and 800 μg TNF/kg BW. The single injection of 200 μg TNF/kg significantly reduced (all P < 0.05) serum TSH, T4) free T4, T3, and hypothalamic TRH compared to the corresponding hormone levels in saline-injected control rats. Serum TSH and hypothalamic TRH recovered to normal levels after 5 days of 150 μg/kg TNF treatment. With the increasing daily doses of TNF, serum TSH and hypothalamic TRH fell significantly. Hepatic 5′ -deiodinase activity was reduced after 1 day of TNF treatment, but increased after the 3-day series of injections. TNF treatment reduced pituitary TSHβ mRNA, but did not affect a-subunit mRNA. TNF treatment also reduced thyroid I25I uptake and reduced thyroidal release of T4 and T3 in response to bovine TSH, but did not change the TSH response to TRH. TNF treatment reduced the binding of pituitary TSH to Concanavalin-A, indicating that it alters the glycosylation of TSH. The TSH with reduced affinity for this lectin had reduced biological activity when tested in cultured FRTL-5 rat thyroid cells. In vitro, TNF inhibited 125I uptake by cultured FRTL-5 rat thyroid cells and blocked the stimulation of [3H]thymidine uptake by these cells. The data indicate that TNF acts on the HPT axis at multiple levels and suggest that TNF is one of the mediators responsible for alterations in thyroid function tests in patients with nonthyroidal illnesses.
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A number of reports have suggested that the spleen plays a key role in the regulation of immunity to malaria but the role, if any, of other tissues is less clear. Furthermore, numerous functional changes occur in the spleen following malaria infection and it is not known whether the spleen’s role relates primarily to its content of malaria‐specific lymphocytes or to the altered structure and function that has occurred. To address these issues we have generated splenic chimeras by transplanting spleens between Plasmodium berghei ‐immune and naive rats. In the absence of a functional spleen, specific immune responses from both isolated splenic and non‐splenic cells can partially control infection. However, an immune spleen in a naive rat can solidly protect the animal from malaria and a normal spleen in an otherwise immune rat can provide enhanced protection over the non‐splenic state. Thus, in the presence of functional splenic architecture both splenic and non‐splenic malaria‐specific lymphocytes operate more effectively. However, these studies do demonstrate an important role for non‐splenic tissue in immunity at least for P. berghei in the rat. The study could have important implications for induction of protective immune responses by vaccination and suggests that malaria‐specific lymphocyte responses induced in the periphery following vaccination could interact with parasites in both spleen‐dependent and spleen‐independent ways.
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Objective To find out the effects of the Qi-Zhu modifying medicine on the immune system of mice in vivo and in vitro.Methods The thymus and spleen index of mice were detected and calculated by directly weighing the immune organs; Phagocytosis of mononuclear macrophage was determined by detecting the content change of the carbon particle in blood.ANAE(+) cell percentage of peripheral blood lymphocytes of mice treated with the QZ medicine was also detected; Spectrophotography was used to estimate the levels of the serum IgG and IgM of mice immunized by SRBC; The delayed type hypersensitivity (DTH) reaction in mice was measured; ConA-induced splenocyte proliferation in mice was assayed by the MTT method.Results The medicine increased significantly the weights of immune organs of young mice.The thymus index in immunosuppression mice induced by Cy showed evident increment by the lower dose of QZ.QZ medicine ((10 g·kg~(-1)) and (20 g·kg~(-1))) increased strikingly the ANAE(+) cell percentage.The QZ medicine ((22.8 g·L~(-1))) enhanced splenocyte proliferation induced by ConA in mice in vitro.Conclusion The QZ medicine can regulate the immune reaction related to T lymophocytes and has no evident effects on phagocytic function of macrophages.edicinei
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ABSTRACT The bacterial growth and the production of tumor necrosis factor alpha (TNF-α) and TNF receptors (TNF-Rs) in the spleen and blood of BALB/c mice challenged with Mycobacterium avium complex (MAC) were monitored. Infection developed in two phases: the first, up to day 21, was associated with rapid MAC multiplication in the spleen and a drop in the mycobacteremia, and the second was associated with control of the infection in both compartments. In the spleen, TNF-α and TNF-RII mRNA levels peaked on day 21 and then slowly decreased; however, no increase in the level of TNF-RI mRNA was observed throughout these experiments. The level of circulating soluble TNF-RII (sTNF-RII) was transiently increased after day 21. In a model in which overproduction of bioactive TNF-α was triggered in response to a second infection with MAC, an increased production of sTNF-RII by cultured splenocytes was also observed. Administration of an antagonist anti-TNF-RII monoclonal antibody (MAb 6G1) to infected mice inhibited the bacterial growth in the spleen, suggesting that the TNF-RII and/or sTNF-RII was functionally involved in the mechanisms that control the infection. Overall, these observations suggest that upregulation of TNF-RII or sTNF-RII contributes to modulation of the TNF-α antibacterial activity in MAC infections.
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Basic parameters of spleen immune activity (spleen weight, histomorphology of splenic compartments, and mitogen-induced splenocyte proliferative capacity in vitro) were evaluated in adult individuals of wild Norway rats from urban habitats and compared to the same data obtained in laboratory rat strains. A wider range of relative spleen mass and differential histomorphological characteristics, together with differences in the level and pattern of responsiveness of splenocytes to exogenous stimulation, were noted in spleens of wild Norway rats. Evidence of both enhanced and low-level immune-relevant spleen activity in wild rats demonstrates the complexity of changes in spleen immune activity in rats from natural populations.
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