TY - JOUR
T1 - IL-13 and IFN-γ
T2 - Interactions in lung inflammation
AU - Ford, J. G.
AU - Rennick, D.
AU - Donaldson, D. D.
AU - Venkayya, R.
AU - McArthur, C.
AU - Hansell, E.
AU - Kurup, V. P.
AU - Warnock, M.
AU - Grünig, G.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2001/8/1
Y1 - 2001/8/1
N2 - 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-γ 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-γ-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-γ would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-γ inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-γ and IL-13 potentiated each other's effects. In the airways of mice given IL-13 and IFN-γ, 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-γ 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.
AB - 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-γ 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-γ-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-γ would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-γ inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-γ and IL-13 potentiated each other's effects. In the airways of mice given IL-13 and IFN-γ, 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-γ 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.
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U2 - 10.4049/jimmunol.167.3.1769
DO - 10.4049/jimmunol.167.3.1769
M3 - Article
C2 - 11466402
AN - SCOPUS:0035424808
SN - 0022-1767
VL - 167
SP - 1769
EP - 1777
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -