Abstract
We investigated whether CTLA4-Ig can reverse established asthma manifestations in a novel murine model of ongoing disease. In BALB/c mice, sensitized to ovalbumin (OVA) without adjuvant, airway inflammation was induced by a first series of OVA aerosol challenges. Murine CTLA4-IgG was then administered, followed by a second series of OVA inhalations. In control-treated mice, two series of OVA challenges induced upregulation of OVA-specific IgE in serum, eosinophils in the bronchoalveolar lavage fluid (BALF), and IL-5 production by lung lymphocytes upon OVA restimulation in vitro, compared with saline-challenged mice. CTLA4-IgG significantly inhibited all of these parameters in OVA-challenged mice. Importantly, mCTLA4-IgG performed better than the gold-standard dexamethasone because this corticosteroid did not inhibit the upregulation of OVA-specific IgE in serum. In a more "severe" ongoing model, induced by sensitization to OVA emulsified in aluminum hydroxide, resulting in airway hyperresponsiveness to methacholine and stronger inflammatory responses, mCTLA4-IgG was less effective in that only the number of eosinophils in the BALF was reduced (P = 0.053), whereas dexamethasone inhibited both BALF eosinophilia and cytokine production by lung lymphocytes. Thus, CTLA4-Ig might be an effective alternative therapy in established allergic asthma, especially in situations of mild disease.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Abatacept
-
Aerosols
-
Allergens / administration & dosage
-
Allergens / immunology
-
Aluminum Hydroxide
-
Animals
-
Anti-Asthmatic Agents / therapeutic use*
-
Anti-Inflammatory Agents / therapeutic use
-
Antigens, CD
-
Antigens, Differentiation / therapeutic use*
-
Asthma / blood
-
Asthma / drug therapy*
-
Asthma / immunology
-
Bronchial Hyperreactivity / chemically induced
-
Bronchial Hyperreactivity / immunology
-
Bronchoalveolar Lavage Fluid / cytology
-
CTLA-4 Antigen
-
Cells, Cultured / immunology
-
Cells, Cultured / metabolism
-
Cytokines / biosynthesis
-
Cytokines / genetics
-
Dexamethasone / therapeutic use
-
Disease Models, Animal
-
Emulsions
-
Eosinophils / immunology
-
Immunization / methods
-
Immunoconjugates*
-
Immunoglobulin E / blood
-
Immunoglobulin E / immunology
-
Immunosuppressive Agents / therapeutic use*
-
Interleukin-5 / biosynthesis
-
Interleukin-5 / genetics
-
Leukocyte Count
-
Lung / immunology
-
Lung / pathology
-
Male
-
Methacholine Chloride
-
Mice
-
Mice, Inbred BALB C
-
Nasal Provocation Tests
-
Ovalbumin / administration & dosage
-
Ovalbumin / immunology
-
Specific Pathogen-Free Organisms
-
T-Lymphocyte Subsets / drug effects
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
Substances
-
Aerosols
-
Allergens
-
Anti-Asthmatic Agents
-
Anti-Inflammatory Agents
-
Antigens, CD
-
Antigens, Differentiation
-
CTLA-4 Antigen
-
Ctla4 protein, mouse
-
Cytokines
-
Emulsions
-
Immunoconjugates
-
Immunosuppressive Agents
-
Interleukin-5
-
Methacholine Chloride
-
Immunoglobulin E
-
Aluminum Hydroxide
-
Abatacept
-
Dexamethasone
-
Ovalbumin