title: Il-13 and IFN-gamma: interactions in lung inflammation.
abstract: Chronic inflammatory diseases of the lungs, such as asthma, are frequently associated with mixed (Th2 and Th1) T cell responses. We examined the impact of critical Th1 and Th2 cytokines, IFN-gamma and IL-13, on the responses in the lungs. In a mouse model of airway inflammation induced by mixed T cell responses, the number of Th1 (IFN-gamma-positive) cells was found to be negatively correlated with airway hyperreactivity. In these mice, blockade of IL-13 partially inhibited airway hyperreactivity and goblet cell hyperplasia but not inflammation. In contrast, in mice that responded with a polarized Th2 response to the same Ag, blockade of IL-13 inhibited airway hyperreactivity, goblet cell hyperplasia, and airway inflammation. These results indicated that the presence of IFN-gamma would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-gamma inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-gamma and IL-13 potentiated each other's effects. In the airways of mice given IL-13 and IFN-gamma, levels of IL-6 were increased as well as numbers of NK cells and of CD11c-positive cells expressing MHC class II and high levels of CD86. In conclusion, IFN-gamma has double-sided effects (inhibiting some, potentiating others) on IL-13-induced changes in the lungs. This may be the reason for the ambiguous role of Th1 responses on Th2 response-induced lung injury.
authors.affiliation: Department of Medicine, Harlem Hospital Center, Harlem Lung Center, Columbia University, New York, NY 10037, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Ford
authors.forename: D
authors.initials: D
authors.lastname: Rennick
authors.forename: D D
authors.initials: DD
authors.lastname: Donaldson
authors.forename: R
authors.initials: R
authors.lastname: Venkayya
authors.forename: C
authors.initials: C
authors.lastname: McArthur
authors.forename: E
authors.initials: E
authors.lastname: Hansell
authors.forename: V P
authors.initials: VP
authors.lastname: Kurup
authors.forename: M
authors.initials: M
authors.lastname: Warnock
authors.forename: G
authors.initials: G
authors.lastname: Grünig
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004357:Drug Synergism; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006131:Growth Inhibitors / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006965:Hyperplasia; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000502:physiology*; D018793:Interleukin-13 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000637:transplantation
chemical_list: D000485:Allergens; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; D018793:Interleukin-13; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D007371:Interferon-gamma