Resolution of airway inflammation following ovalbumin inhalation: comparison of ISS DNA and corticosteroids.
In this study we have compared the therapeutic effect of the administration of immunostimulatory DNA sequences (ISS) with that of corticosteroids on the resolution of airway inflammation and airway hyperreactivity (AHR) in a mouse model. Mice which had already developed significant levels of eosinophilic airway inflammation 24 h after allergen challenge were then treated with either ISS or corticosteroids, and the effect on AHR and airway inflammation assessed 6 d later. ISS inhibited AHR as effectively as corticosteroids. Combination therapy with ISS and corticosteroids was more effective than monotherapy with either ISS or corticosteroids in inhibiting AHR. In ovalbumin-challenged mice, levels of bronchoalveolar lavage (BAL) eosinophils were significantly reduced with either ISS or corticosteroids. ISS induced significant levels of BAL interferon-gamma, whereas corticosteroids did not induce expression of BAL interferon-gamma. Both ISS and corticosteroids significantly reduced levels of interleukin-5 in BAL, as well as the number of Periodic Acid Schiff-positive airway epithelial cells. Corticosteroids, but not ISS, increased the number of eosinophils in regional mediastinal lymph nodes. Very few apoptotic peribronchial cells were noted following ovalbumin challenge as assessed by TUNEL assay. Corticosteroids, but not ISS, induced an increase in the small number of apoptotic peribronchial cells. The mechanism by which either ISS or corticosteroids inhibit AHR is likely to be mediated by distinct and shared cellular pathways. The combination of the shared and distinct anti-inflammatory pathways may account for the additive effect of ISS and corticosteroids on inhibiting AHR.
Ikeda
Reid K
RK
Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0635, USA.
Nayar
Jyothi
J
Cho
Jae Youn
JY
Miller
Marina
M
Rodriguez
Monica
M
Raz
Eyal
E
Broide
David H
DH
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004247:DNA / Q000276:immunology / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D003907:Dexamethasone; D007371:Interferon-gamma; D010047:Ovalbumin; D004247:DNA