In Vivo Effect of Interleukin-6 on Cycling Status of Hematopoietic Progenitors from Adults and Neonates

Liechty, Kenneth W.; Christensen, Robert D.

doi:10.1203/00006450-199010000-00004

Cited by 12 publications

(3 citation statements)

References 15 publications

(18 reference statements)

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“…Consistent with this evidence, administration of either testosterone or the 11L-6 neutralizing antibody produced a greater decrease in the number dividing CFU-GM as compared to the total number of CFU-GM. These observations are in agreement with evidence that IL-6 promotes differentiation of hematopoietic cells by stimulating cell division of early progenitors (41)(42)(43); moreover, they strengthen the view that the cascade of events leading to bone loss, following loss of sex steroids, starts in the hematopoietic bone marrow.…”

supporting

confidence: 80%

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Bellido¹,

Jilka²,

Boyce³

et al. 1995

J. Clin. Invest.

407

218

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Interleukin-6 is an essential mediator of the bone loss caused by loss of estrogens. Because loss of androgens also causes bone loss, we have examined whether the IL-6 gene is regulated by androgens, and whether IL-6 plays a role in the bone loss caused by androgen deficiency. Both testosterone and dihydrotestosterone inhibited IL-6 production by murine bone marrow-derived stromal cells. In addition, testosterone, dihydrotestosterone, and adrenal androgens inhibited the expression of a chloramphenicol acetyl transferase reporter plasmid driven by the human IL-6 promoter in HeLa cells cotransfected with an androgen receptor expression plasmid; however, these steroids were ineffective when the cells were cotransfected with an estrogen receptor expression plasmid. In accordance with the in vitro findings, orchidectomy in mice caused an increase in the replication of osteoclast progenitors in the bone marrow which could be prevented by androgen replacement or administration of an IL-6 neutralizing antibody. Moreover, bone histomorphometric analysis of trabecular bone revealed that, in contrast to IL-6 sufficient mice which exhibited increased osteoclast numbers and bone loss following orchidectomy, IL-6 deficient mice (generated by targeted gene disruption) did not. This evidence demonstrates that male sex steroids, acting through the androgen-specific receptor, inhibit the expression of the IL-6 gene; and that IL-6 mediates the upregulation of osteoclastogenesis and therefore the bone loss caused by androgen deficiency, as it does in estrogen deficiency. (J.

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supporting

confidence: 80%

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Bellido¹,

Jilka²,

Boyce³

et al. 1995

J. Clin. Invest.

407

218

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“…IL‐6 and TNF‐α are the so‐called endogenous pyrogens (IL‐1, IL‐6 and TNF‐α) involved in innate immune responses. More importantly, IL‐6 induces an increase of circulating neutrophils that are summoned from the bone marrow [26,27]. Such a function of IL‐6 may be of great importance in supporting the expansion of myeloid cells during development.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses

Zhao

Dai

et al. 2002

Clinical and Experimental Immunology

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The phenotypic and functional characteristics of fetal lymphocytes are of considerable interest for our understanding of the development of the immune system. Recent advances demonstrate that prenatal contact of allergens and other antigens is possible and also that the fetal T and B cells might be able to response to various stimuli during gestation [1][2][3][4][5][6]. A potential link between prenatal contact with allergens and allergic disease in future life has also been proposed [1]. Mononuclear cells in the human umbilical cord blood collected after delivery at term have been thoroughly studied in the last two decades [7][8][9][10][11][12][13][14] and it is generally accepted that T cells from the neonates are phenotypically and functionally immature. However, currently little is known about the maturational process of fetal T cells during human gestation, due to the difficulties in obtaining, and also ethical dilemmas of working with, human fetal tissues. So far, only a handful of reports documented the phenotypes of T lymphocytes in human fetuses [15][16][17][18][19][20][21], few covered the functional status of these cells [1,2,6].T cells are identified by monoclonal Ab against CD3 and are further divided into CD4 + (helper) and CD8 + (cytotoxic) subsets. The majority of peripheral T cells express ab-TCR, while a small proportion (about 10%) express gd-TCR. CD16 and CD56 are commonly used for the identification of NK cells that do not have T cell surface markers. In the present study, we collected blood samples by ultrasound-guided cordocentesis from umbilical cord of human fetuses at early second-and third-trimester. Phenotypes of the T cell subsets were quantitatively determined by flow cytometry and their functional status analysed in proliferation and cytokine (IL-2, IL-4, IL-16, IL-10, TNF-a and IFN-g) assays.Term cord blood, maternal and healthy unrelated male adult peripheral blood samples were also included as controls. MATERIALS AND METHODS Subjects and blood samples SUMMARYThis study was undertaken to investigate the phenotypic and functional status of T lymphocytes of human fetuses from early second-to third-trimester. Cord blood samples were obtained from 19 healthy human fetuses (gestation weeks: 18-36), by cordocentesis, and 16 term newborns (gestation weeks 37-42). Maternal and unrelated male blood samples were also taken as controls. Percentage of lymphocytes in fetal white blood cells was 79·3%, reducing to 40% by term birth, much higher than that of adults. Cord blood mononuclear cells (CBMC), prepared by density gradient centrifugation followed by lysis of erythrocytes, were stained using PE-or FITC-labelled monoclonal Abs and analysed by flow cytometry. The frequencies of CD3 + T cells in fetal (40·1%) and neonatal (42·4%) CBMC were significantly lower than that of men (59·6%) and pregnant women (53·6%). Proportions of CD8 + T cells (9·5%), gd-T cells (0·5%) and NK cells (4·8%) in fetal CBMC were also lower than that of neonates (except gd-T cells) and adults. A negative linear corr...

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“…An important function of IL-6 is the induction of haematopoietic progenitors from stationary phase (Go-phase) into active cycling both in-vitro (14,15), and in-vivo (16,17).…”

Section: Qrupabo Hay and Evansmentioning

confidence: 99%

Effect of Metals on Interleukin-6 (IL-6) Mitogenic Stimulation of Murine Hybridoma Cells

Orupabo

Hay

Evans

1992

Immunopharmacology and Immunotoxicology

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The effect of several divalent metal cations (Co, Cu, Zn, Hg and Pb) on the proliferative response of B9 hybridoma cells to IL-6 has been investigated. At concentrations which are not cytotoxic all the metals inhibited proliferation. The inhibition by Cd and Pb was dependent on both time of addition of the metal and IL-6 concentration. Cd (10 microM) and Pb (50 microM) added at the same time as IL-6 were inhibitory but added 24h later had no effect. Increasing the concentration of IL-6 overcame the inhibitory effect of Cd (10 microM) and Pb (50 microM). Inhibition caused by the other metals was independent of either time of addition or IL-6 concentration. IL-6 did not stimulate an increased intracellular concentration of metallothionein suggesting that the protective effect of IL-6 is not mediated via induction of metallothionein. The results suggest that there are at least two distinct metal sensitive events in B9 proliferation, i) IL-6 reversible inhibition by Cd and Pb ii) IL-6 independent inhibition by Co, Cu and Hg.

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In Vivo Effect of Interleukin-6 on Cycling Status of Hematopoietic Progenitors from Adults and Neonates

Cited by 12 publications

References 15 publications

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses

Effect of Metals on Interleukin-6 (IL-6) Mitogenic Stimulation of Murine Hybridoma Cells

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