Mechanisms of asthma and allergic inflammationCyclophosphamide augments inflammation by reducing immunosuppression in a mouse model of allergic airway disease
Section snippets
Animals
Female BALB/c mice, 6-8 weeks old, were obtained from Animal Resources Centre (Perth, Australia). All animals were housed in pathogen-free conditions at the Garvan Institute of Medical Research. All experiments were approved by the Garvan/St Vincent's Animal Experimentation Ethics Committee and conducted according to the animal welfare guidelines of the National Health and Medical Research Control of Australia.
Induction of asthma and administration of cyclophosphamide
Mice were immunized and boosted by intraperitoneal injection of 100 μg ovalbumin
Cyclophosphamide exacerbated lung inflammation
Mice were immunized twice with ovalbumin and challenged 4 times by inhalation of aerosolized ovalbumin. Lung histology was assessed 24 hours after the last challenge. In these mice (ovalbumin group), high-power examination revealed significant cellular infiltration including numerous eosinophils in the perivascular and peribronchial areas (Fig 1, A). Sections of ovalbumin-immunized and challenged mice given 2 injections of cyclophosphamide (CY/OVA group) showed a much more pronounced cellular
Discussion
We have demonstrated that administration of cyclophosphamide was followed by increased airway allergic inflammation in a mouse model. Features increased by cyclophosphamide included eosinophilia in the lung tissue (Fig 1) and BAL fluid (Fig 2), serum IgE, and production of TH2 effector cytokines, IL-4 and IL-5 (Fig 3). The features augmented by cyclophosphamide are all consistent with a TH2 response. Cyclophosphamide is well known to augment TH1-mediated autoimmune diseases and other TH
References (33)
- et al.
The role of T lymphocytes in the pathogenesis of asthma
J Allergy Clin Immunol
(2003) - et al.
Allergy and asthma
J Allergy Clin Immunol
(2005) - et al.
Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity
J Allergy Clin Immunol
(2003) - et al.
Regulatory T cells control the development of allergic disease and asthma
J Allergy Clin Immunol
(2003) - et al.
Inhibition of CD4+CD25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide
Blood
(2005) - et al.
Islet T cells secreting IFN-gamma in NOD mouse diabetes: arrest by p277 peptide treatment
J Autoimmun
(1998) - et al.
Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Treg cells
Blood
(2005) - et al.
Asthma: an epidemic of dysregulated immunity
Nat Immunol
(2002) - et al.
Airway remodeling in asthma: new insights
J Allergy Clin Immunol
(2003) Immunologic basis of antigen-induced airway hyperresponsiveness
Annu Rev Immunol
(1999)
Regulation of delayed-type hypersensitivity reactions by cyclophosphamide-sensitive T cells
J Immunol
Pre-existing tumor-sensitized T cells are essential for eradication of established tumors by IL-12 and cyclophosphamide plus IL-12
J Immunol
Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice
Eur J Immunol
CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative
Eur J Immunol
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases
J Immunol
CD4+ Tregs and immune control
J Clin Invest
Cited by (0)
Supported by the Cooperative Research Center for Asthma and by Infrastructure Grants from the New South Wales State Health Department. Dr Su is funded by an Endeavour International Postgraduate Research Scholarship from the Faculty of Medicine, University of New South Wales.