title: Nebulized but not parenteral IFN-gamma decreases IgE production and normalizes airways function in a murine model of allergen sensitization.
abstract: An animal model of local allergen (airways) sensitization was employed to study the effects of rIFN-gamma administered by ultrasonic nebulization through the airways on IgE production and airways responsiveness. BALB/c mice exposed to aerosolized OVA daily for 10 days developed a predominant anti-OVA IgE response, immediate cutaneous reactivity to OVA, and increased airways responsiveness (AR). Mice were treated with rIFN-gamma, either systemically or locally via the airways, following different protocols; i.p. rIFN-gamma failed to modulate the course of OVA sensitization, although total IgE levels in the serum were decreased by 50%. Anti-OVA IgE levels remained elevated, immediate skin test responses to OVA persisted, and AR was increased. However, local treatment of the airways with nebulized rIFN-gamma caused a 66% decrease in serum anti-OVA IgE and a twofold rise in IgG2a levels. Cutaneous reactivity to OVA was reduced and AR was also normalized after nebulized rIFN-gamma. In contrast to the i.p. route, treatment with nebulized rIFN-gamma resulted in a reduction in the in vitro IgE production by lymphocytes in response to OVA and IL-4. The timing of treatment with nebulized rIFN-gamma was important in determining the immunomodulatory response. Treatment after day 7 of OVA exposure failed to modulate sensitization. Treatment regimens with nebulized rIFN-gamma that began before day 7 of OVA exposure were able to decrease anti-OVA IgE. Only treatment regimens that included 3 days of nebulized IFN-gamma before OVA sensitization caused a decrease in cutaneous reactivity and normalization of AR. The data demonstrate that both the route and timing of rIFN-gamma administration are critical factors in the immunomodulation of the immediate allergic response to allergen sensitization via the airways.
authors.affiliation: Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: G
authors.initials: G
authors.lastname: Lack
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: J
authors.initials: J
authors.lastname: Saloga
authors.forename: K L
authors.initials: KL
authors.lastname: Bradley
authors.forename: J
authors.initials: J
authors.lastname: Loader
authors.forename: D Y
authors.initials: DY
authors.lastname: Leung
authors.forename: G
authors.initials: G
authors.lastname: Larsen
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000336:Aerosols; D000485:Allergens; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001682:Biological Availability; D004195:Disease Models, Animal; D006969:Hypersensitivity, Immediate / Q000517:prevention & control* / Q000628:therapy; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins; D012137:Respiratory System / Q000276:immunology*; D012867:Skin / Q000276:immunology
chemical_list: D000336:Aerosols; D000485:Allergens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin