Der Einfluss von Methylprednisolon auf Migration und Subpopulationen humaner Monozyten

by Tobias Lukas Klaus Finck
Doctoral thesis
Date of Examination:2022-05-11
Date of issue:2022-05-10
Advisor:PD Dr. Fred Lühder
Referee:Prof. Dr. Dieter Kube
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-9235

 

 

Files in this item

Name:Thesis Tobias Finck final EDISS 04.05.22 ohn...pdf
Size:3.79Mb
Format:PDF

The following license files are associated with this item:

Abstract

English

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). One of its hallmarks is the infiltration of mononuclear cells into the CNS and inflammation of the brain. Among other cells of the immune system, monocytes play an important role in the pathogenesis of the disease. In addition to their supporting function as antigen-presenting cells, they exert independent functions that, on the one hand, lead to tissue damage and progression of the disease. On the other hand, however, monocytes also possess regulatory capabilities that can promote anti-inflammation and tissue repair. Glucocorticoids (GCs), in clinical routine mostly methylpednisolone, are the standard of care for acute relapses in MS patients. Their effects on the immune system are diverse and their exact mechanisms of action remain the subject of ongoing research. An effect on monocyte polarization is already known. In the present work, we investigated the effects of methylprednisolone (MP) on monocytes from healthy volunteers and MS patients in vitro and in vivo. The subpopulations of monocytes in the blood of MS patients differed from those of healthy subjects. The subpopulations were only slightly affected by treatment with MP. Chemotaxis of monocytes toward CCL2, CCL5, and CX3CL1 was elevated in MS patients compared with healthy individuals and was further enhanced by MP pulse therapy, especially toward proinflammatory chermokines. The pro-migratory effects were more pronounced in MS patients with an acute relapse than in patients with progressive disease course. Intriguingly, the migration-promoting effect of MP was not dependent on chemokine receptor levels, as shown by the exemplary results for CCR2. Overall, our results suggest that GCs induce an anti-inflammatory monocyte phenotype and promote the migration of these monocytes into the inflamed CNS, where they attenuate the pathogenic immune response.
Keywords: Multiple Sclerosis; Monocytes; chemokines; methylprednisolone therapy; m2 polarization
 
Statistik