title: Effect of inhaled and systemic glucocorticoid treatment on CD4+regulatory and effector T cells in a mouse model of allergic asthma.
abstract: To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4+T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4+effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4+Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4+Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4+Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4+T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4+T cells.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland. Electronic address: monika.zuska@gmail.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Zuśka-Prot
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland. Electronic address: tomasz.maslanka@uwm.edu.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Maślanka
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011282:Pregnenediones / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; D010047:Ovalbumin; C120481:ciclesonide; D008775:Methylprednisolone
keywords: Apoptosis; Asthma; CD4(+) T cells; Glucocorticoids; Proliferation; Regulatory T cells