Differential role of IFN-gamma-inducible protein 10 kDa in a cockroach antigen-induced model of allergic airway hyperreactivity: systemic versus local effects.
The ability of IFN-gamma to antagonize established Th2 type allergic responses is well documented. To investigate the role of IFN-gamma-inducible protein 10 kDa (IP10) in the allergic response, we chose to investigate the effect of IP10 neutralization on an established Th2 response. Systemic neutralization of IP10 at the time of allergen challenge increased airway hyperreactivity as well as airway eosinophil accumulation. Interestingly, IFN-gamma levels were markedly reduced in both the lung and peripheral lymph node following IP10 neutralization. Furthermore, the number of CXCR3(+)CD4(+) T cells was decreased in the peripheral lymph node following neutralization of IP10. Introduction of exogenous IP10 into the airway at the time of allergen challenge also dramatically increased eosinophil accumulation in the airway. Protein levels of IL-4, IL-5, and IL-13 were significantly increased in the lung following exogenous airway administration of IP10 with allergen. Interestingly, airway hyperreactivity was significantly decreased at early time points following concurrent IP10 and allergen challenge but rebounded at 24 and 48 h post allergen challenge. Although IP10 may initially be acting locally to dampen the allergic response, its ability to recruit eosinophils may ultimately supersede any immunomodulatory effect it may have in an established allergic response. These results suggest that while systemic levels of IP10 are beneficial in controlling the allergic response, possibly by regulating cellular trafficking in the lymph node, local administration of exogenous IP10 into an established allergic response may be detrimental.
Thomas
Molly S
MS
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Kunkel
Steven L
SL
Lukacs
Nicholas W
NW
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D003058:Cockroaches / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007371:Interferon-gamma / Q000502:physiology*; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D052179:Antigens, Plant; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D007106:Immune Sera; C060835:allergen CRa, cockroach; D007371:Interferon-gamma