Cytokines mediate protective stimulation of glucocorticoid output during autoimmunity: involvement of IL-1

1998 ◽  
Vol 275 (4) ◽  
pp. R1146-R1151 ◽  
Author(s):  
Adriana Del Rey ◽  
Isabel Klusman ◽  
Hugo O. Besedovsky
Keyword(s):  
Basic Protein ◽  
Interleukin 1 ◽  
Endocrine Response ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Pituitary Adrenal Axis ◽  
Experimental Autoimmune ◽  
Stimulation Of

Endogenous glucocorticoid levels are increased during experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Although this endocrine response is essential for survival, the mechanism that triggers the stimulation of glucocorticoid output during the disease remains unknown. We report here that 1) after immunization with the encephalitogenic antigen myelin basic protein (MBP), increased blood glucocorticoid levels are not only observed in Lewis rats, but also in PVG rats, which do not develop EAE; 2) immune cells obtained from animals with EAE and stimulated in vitro with MBP produced mediators that increased glucocorticoid levels when administered to naive recipients; and 3) acute in vivo blockade of interleukin-1 (IL-1) receptors inhibited, to a large extent, the increase in corticosterone levels during EAE. These results show that the increase in corticosterone levels after immunization with MBP can be dissociated from the stress of the paralytic attack that characterizes EAE. Furthermore, they indicate that an endocrine response, which is decisive for the prevention or moderation of EAE, is mainly the result of the stimulation of the hypothalamic-pituitary-adrenal axis by cytokines produced during the immune response that induces the autoimmune disease.

scholarly journals Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

2005 ◽  
Vol 202 (3) ◽  
pp. 445-455 ◽  
Author(s):  
Niklas Beyersdorf ◽  
Stefanie Gaupp ◽  
Karen Balbach ◽  
Jens Schmidt ◽  
Klaus V. Toyka ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Subset ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo and upon short-term in vitro culture. Here we demonstrate that application of very low dosages of the CD28 superagonist into normal Lewis rats is sufficient to induce T reg cell expansion in vivo without the generalized lymphocytosis observed with high dosages of JJ316. Single i.v. administration of a low dose of the CD28 superagonist into Dark Agouti (DA) rats or Lewis rats that suffered from experimental autoimmune encephalomyelitis (EAE) proved to be highly and equally efficacious as high-dose treatment. Finally, we show that T reg cells that were isolated from CD28-treated animals displayed enhanced suppressive activity toward myelin basic protein–specific T cells in vitro, and, upon adoptive transfer, protected recipients from EAE. Our data indicate that this class of CD28-specific monoclonal antibodies targets CD4+CD25+ T reg cells and provides a novel means for the effective treatment of multiple sclerosis and other autoimmune diseases.

Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1 beta infusion: in vivo and in vitro studies.

Endocrinology ◽  
1992 ◽  
Vol 130 (3) ◽  
pp. 1153-1164
Author(s):  
C G Sweep ◽  
M J van der Meer ◽  
A R Hermus ◽  
A G Smals ◽  
J W van der Meer ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
In Vitro Studies ◽  
Interleukin 1 Beta ◽  
Chronic Stimulation ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis ◽  
Stimulation Of

scholarly journals Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hélène Letscher ◽  
Viviane A. Agbogan ◽  
Sarantis Korniotis ◽  
Pauline Gastineau ◽  
Emmanuel Tejerina ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Toll Like Receptor ◽  
Hematopoietic Progenitors ◽  
Autoimmune Encephalomyelitis ◽  
Hematopoietic Precursor ◽  
Therapeutic Properties ◽  
Experimental Autoimmune

AbstractEarly innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.

scholarly journals Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

2017 ◽  
Vol 214 (4) ◽  
pp. 905-917 ◽  
Author(s):  
Yochai Wolf ◽  
Anat Shemer ◽  
Michal Polonsky ◽  
Mor Gross ◽  
Alexander Mildner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mononuclear Phagocytes ◽  
Autoimmune Encephalomyelitis ◽  
Wild Type Counterpart ◽  
And Function ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

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