Administration of glucocorticoids markedly increases the numbers of granulocytes and extrathymic T cells in the bone marrow.
Glucocorticoids, steroid hormones, are widely used as an anti-inflammatory drug. However, clinicians have sometimes encountered adverse drug reactions such as ulcers and tissue damage. In this study, we investigated how such adverse reactions of glucocorticoids are evoked, using an experimental mice model. When hydrocortisone (0.5 or 1.0 mg/day/mouse) was administered daily for 2 weeks, severe leukocytopenia was induced in all immune system organs. However, granulocytes (Gr-1(+)Mac-1(+)) were increased in number in the bone marrow and peripheral blood. This seemed to be due to an elevated level of myelopoiesis in the bone marrow. As well as increasing in number, granulocytes were functionally activated as estimated by the Ca2+ influx and superoxide production. The proportion of primordial T cells (CD3(int)IL-2Rbeta+) in the thymus and the number of primordial T cells in the bone marrow also increased. Mice administered hydrocortisone became susceptible to stress. Thus, these mice showed gastric ulcers when they were exposed to restraint stress for 12 h. These results suggest that activated granulocytes and primordial T cells might provide a mechanism involved in steroid ulcers and tissue damage, possibly through the superoxide production of granulocytes and the autoreactivity of primordial T cells.
Maruyama
S
S
Department of Immunology, Niigata University School of Medicine, Niigata, Japan.
Minagawa
M
M
Shimizu
T
T
Oya
H
H
Yamamoto
S
S
Musha
N
N
Abo
W
W
Weerasinghe
A
A
Hatakeyama
K
K
Abo
T
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D017252:CD3 Complex; D002395:Catecholamines / Q000097:blood; D002452:Cell Count; D002478:Cells, Cultured; D004351:Drug Resistance; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007694:Killer Cells, Natural; D007970:Leukopenia / Q000139:chemically induced; D008099:Liver / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland
D000893:Anti-Inflammatory Agents; D017252:CD3 Complex; D002395:Catecholamines; D005938:Glucocorticoids; D006854:Hydrocortisone