The stimulatory effects of interleukin (IL)-12 on hematopoiesis are antagonized by IL-12-induced interferon gamma in vivo
| Autor: | M. Lorenz, T. D. Anderson, B. Schnyder, V. F. J. Quesniaux, Michel Aguet, Bruce D. Car, V. M. Eng, Bernhard Ryffel, S. M. Lugli |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_treatment
Immunology Interleukin Articles Biology medicine.disease Interleukin-12 Extramedullary hematopoiesis Hematopoiesis Haematopoiesis Interferon-gamma Mice Cytokine medicine.anatomical_structure Interferon Bone Marrow medicine Interleukin 12 Immunology and Allergy Animals Interferon gamma Bone marrow medicine.drug Receptors Interferon |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Interleukin (IL)-12 synergizes with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors in vitro. However, in vivo administration of IL-12 decreases peripheral blood counts and bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor-deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12 administered for 4 d (1 microgram/mouse per day) resulted in lower peripheral blood counts and a 2-fold decrease in bone marrow cellularity in wild-type mice, but not in IFN gamma R-/- mice. Bone marrow hematopoietic progenitors were decreased after IL-12 treatment in wild-type mice, but rather increased in IFN gamma R-/- mice. Splenic cellularity was 2.3-fold higher after IL-12 administration in wild-type mice, largely due to natural killer (NK) cell and macrophage infiltration together with some extramedullary hematopoiesis. In IFN gamma R-/- mice, spleen cellularity was less increased, there were fewer infiltrating NK cells, but a strong extramedullary hematopoiesis. Thus, alterations mediated by IL-12-induced IFN-gamma include reduction in bone marrow cellularity and hematopoietic progenitors, as well as pronounced splenomegaly, largely caused by NK cell infiltration. In the absence of IFN-gamma signaling, IL-12 promotes hematopoiesis, consistent with its in vitro activities. |
| Databáze: | OpenAIRE |
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