Administration of Glucocorticoids Markedly Increases the Numbers of Granulocytes and Extrathymic T Cells in the Bone Marrow

Maruyama, Satoshi; Minagawa, Masahiro; Shimizu, Takao; Oya, Hiroshi; Yamamoto, Satoshi; Musha, Nobuyuki; Abo, Wataru; Weerasinghe, Anura; Hatakeyama, Katsuyoshi; Abo, Toru

doi:10.1006/cimm.1999.1492

Cited by 32 publications

(23 citation statements)

References 46 publications

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“…This would seem to indicate that the oxidized substance stimulates tissues and infiltration by granulocytes occurs. We confirmed this phenomenon in an animal model (7). Oxidized cholesterols directly induce the accumulation of granulocytes at the corresponding sites (our unpublished observation).…”

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confidence: 78%

Stagnation of Steroid Hormones in Patients with Atopic Dermatitis and Unique Variation of Leukocyte Pattern during the Withdraival Syndrome after Cessation of Steroid Ointment

et al. 2003

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Patients with severe atopic dermatitis are sometimes seen even after 15-20 years of age, despite tl1e fact that this is age when atopic dermatitis subsides in usual cases. We consider the possibility that steroid hormones administered as ointment stagnate in the skin and become oxidized cholesterols. Such substances may induce circulation failure and granulocyte-associated inflammation. We herein report the withdrawal of the above ointment in such patients, resulting in successful treatment within several months. Since they suffered from the withdrawal syndrome for the first two or three weeks, acupuncture was performed. Before therapy, these patients showed elevated levels of granulocytes and eosinophils, and an inverse decreased level of lymphocytes in the blood. The number and proportion of granulocytes are known to increase by sympathetic nerve stimulation.This, therefore, indicated that these patients were in a dominant state of the sympathetic nervous system. During the therapy, this leukocyte pattern became much worse due to the withdrawal syndrome. However, in parallel with the amelioration of inflammation, normalization of the leukocyte pattern was observed. These results revealed that, by some yet-undetermined reasons, patients with atopic dermatitis who had been treated by steroid ointment for long time, showed an unusual pattern of leukocytes (i.e., granulocytosis) and that this leukocyte pattern was normalized by the withdrawal of steroid hormones in parallel with the amelioration of the disease.The onset of atopic dermatitis usually begins at infancy or childhood and some cases experience spontaneous cure before adolescence (3, 12). Primarily, people in childhood show a predominant state of the immune system (i.e., a high level of lymphocytes) (5). However", adults gradually show a decreased level of the immune system (9). The level of granulocytes surpasses that of lymphocytes at l5~20 years old in Japan (our unpublished observation). We speculate that this age-associated change of the Correspondence to: Dr. T. Abo, Department of Immunology, Niigata University School of Medicine, Asahimachi-dori 1, Niigata 951-8510, Japan Fax: + 81-25-227-0766 E-mail: immunol2@med.niigata-u.ac.jp immune system might be responsible for the spontaneous cnre of atopic dermatitis. In other words, many cases of atopic dermatitis naturally subside due to an age-dependent decrease in the number of T cells.

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confidence: 78%

Stagnation of Steroid Hormones in Patients with Atopic Dermatitis and Unique Variation of Leukocyte Pattern during the Withdraival Syndrome after Cessation of Steroid Ointment

et al. 2003

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“…However, Barr et al (1983) reported that hydrocortisone exhibited a dose-dependent effect on cfu-GM proliferation in vitro (i.e., enhancement at low concentrations and inhibition at high concentrations). In contrast, more recent studies demonstrated increased numbers of granulocytes not only in circulation, but also in the bone marrow, indicating that myelopoiesis is enhanced by in vivo administration of hydrocortisone (Maruyama et al, 1999;Laakko and Fraker, 2002).…”

Section: Discussionmentioning

confidence: 86%

Differential Effects of Steroids and Retinoids on Bovine Myelopoiesis in Vitro

Merris

Meyer

Duchateau

et al. 2004

Journal of Dairy Science

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Pregnancy and parturition are associated with physiological changes caused by steroid hormones. Alterations in number, maturity, and function of polymorphonuclear leukocytes observed in dairy cows at parturition suggest a common causative relationship with steroid hormones. This study was designed to investigate the effects of progesterone, 17-β-estradiol, and hydrocortisone on the proliferation of bovine progenitor cells. An in vitro culturing system was used, and colonies were scored after 7 d of incubation. At low concentrations, 17-β-estradiol inhibited proliferation of granulocyte progenitor cells. Hydrocortisone reduced growth of granulocyte and monocyte colonies, whereas myelopoiesis was not altered by progesterone. Furthermore, we studied the effect of retinoids on colony formation of bovine bone marrow cells. All-trans-and 9-cis-retinoic acid stimulated growth of granulocyte colonies and inhibited proliferation of the monocyte lineage. The addition of the 13-cis-isomer also increased numbers of granulocyte colony-forming units. This study indicates that steroid hormones may be responsible for alterations in the bovine hematopoietic profiles observed in circulation during the postpartum period. White blood cells, especially polymorphonuclear leukocytes, which are derived from bone marrow, are an important first line defense against mastitis. Therefore, these effects of steroids might contribute to the increased susceptibility of dairy cows to Escherichia coli mastitis. We furthermore hypothesize that an important role might be attributed to retinoic acid in its regulation of bovine myelopoiesis. Modulation of myelopoiesis in favor of the granulocyte lineage during the acute-phase reaction may be an adaptive mechanism designed to increase the capacity of first-line defense to intramammary infections. Received: October 8, 2003. Accepted: November 6, 2003 Corresponding author: C. Burvenich; e-mail: Christian.Burvenich @UGent.be. 1188(Key words: steroid hormone, retinoic acid, bone marrow, myelopoiesis) Abbreviation key: cfu-G = colony-forming unit-granulocyte, cfu-GM = colony-forming unit-granulocyte and monocyte, cfu-M = colony-forming unit-monocyte, cfutotal = colony-forming unit-total myeloid, FBS = fetal bovine serum, IMDM = Iscove's modified Dulbecco's Minimal Essential, PMN = polymorphonuclear leukocytes, RAR = retinoic acid receptor, RXR = retinoid X receptor.

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“…In other words, the applied protocol of hyperthermia in this study was estimated to be a borderline between stress and non-stress. We previously reported that an injection of steroid hormone induces granulocytosis (mainly neutrophils) as well as lymphocytopenia (including thymic atrophy) (9). Granulocytosis is sometimes dangerous in that it induces tissue damage via production of superoxides (6,8).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment

Tomiyama-Miyaji

Watanabe

Ohishi³

et al. 2007

Biomed. Res.

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Since high levels of hyperthermia induce immunosuppression to a certain extent (i.e., granulocytosis and lymphocytopenia) in patients, we applied mild hyperthermia in volunteers using equipment enabling well-controlled hyperthermia. Restricted control of rectal temperature at 39.4 (± 0.2)°C for 30 min was conducted and various parameters of the body were examined. The most prominent change observed during exposure to hyperthermia was elevated levels of pH and PO 2 in the blood, even in the venous blood. A transient elevation of ACTH, cortisol and growth hormone in the blood was also seen during this time. In parallel with this phenomenon, the number of total lymphocytes and those of its subsets (especially CD57 + or CD56 + NK cells and NKT cells) increased. More interestingly, the proportion of HLA-DR (MHC class II antigens) increased in NK and NKT cells, and their intensity on the surface of CD20 + B cells increased. These results suggest that mild hyperthermia is important for modulation of the functions of the circulatory, endocrine and immune systems.It is widely known that hyperthermia induces the production of heat shock proteins (HSPs) and that such HSPs are able to induce immunopotentiation via the augmented expression of MHC class I or II antigens on lymphocytes and tissue cells (2, 3, 10, 15). Hyperthermia is therefore expected to have potential as cancer immunotherapy. Another strategy for use of hyperthermia in cancer therapy is based on the notion that cancer cells are sensitive to thermal stress, which results in apoptotic death (5,20,23). However, we have encountered severe granulocytosis and lymphocytopenia in patients or animals during the exposure to various types of stress, including hyperthermia (4,12,16,17). This experience is contrary to our expectation for immunopotentiation by hyperthermic therapy.In light of these findings, we conducted mild hyperthermia in volunteers using the "Thercura System," a well-controlled hyperthermia device. We found that restricted control of rectum temperature to 39.4 (± 0.2)°C for 30 min was able to induce a prominent potentiation of many parameters in the circulation, endocrine system and immune system. Especially, the immunopotentiation induced by the present protocol of mild hyperthermia seems to be of great value for cancer patients and other diseased persons for treatment of their decreased levels of the immune functions.

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Administration of Glucocorticoids Markedly Increases the Numbers of Granulocytes and Extrathymic T Cells in the Bone Marrow

Cited by 32 publications

References 46 publications

Stagnation of Steroid Hormones in Patients with Atopic Dermatitis and Unique Variation of Leukocyte Pattern during the Withdraival Syndrome after Cessation of Steroid Ointment

Stagnation of Steroid Hormones in Patients with Atopic Dermatitis and Unique Variation of Leukocyte Pattern during the Withdraival Syndrome after Cessation of Steroid Ointment

Differential Effects of Steroids and Retinoids on Bovine Myelopoiesis in Vitro

Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment

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