Alterations in nitric oxide and cytokine production with airway inflammation in the absence of IL-10.
IL-10 is an anti-inflammatory cytokine that suppresses NO synthase (NOS) and production of NO; its lack may promote NO production and alterations in cytokines modulated by NO with allergic airway inflammation (AI), such as IL-18 and IL-4. Therefore, we induced AI in IL-10 knockout ((-/-)) and IL-10-sufficient C57BL/6 (C57) mice with inhaled OVA and measured airway NO production, as exhaled NO (E(NO)) and bronchoalveolar lavage fluid nitrite levels. E(NO) and nitrite levels were elevated significantly in naive IL-10(-/-) mice as compared with C57 mice. With AI, E(NO) and nitrite levels increased in C57 mice and decreased in IL-10(-/-) mice. IL-18 production fell with both AI and addition of S-nitroso-N-acetyl-d,l-penicillamine (a NO donor) but was not significantly increased by chemical NOS inhibition by l-N(5)-(1-iminoethyl)-ornithine. IL-4 AI was increased significantly (up to 10-fold greater) in the absence of IL-10 but was reduced significantly with chemical inhibition of NOS. Airway responsiveness was lower in IL-10(-/-) mice and was associated with alteration in production of NO and IL-4. Thus, IL-4 production was increased, and likely decreased NO production, in a way not predicted by the absence of IL-10. Inhibition of IL-4 production, with inhibition of NOS in the absence of IL-10, demonstrated the importance of a NO and IL-4 feedback mechanism regulating this interaction.
Asthma, Allergy, and Airway Research Center, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, Pittsburgh, PA 15261, USA. ameredesbt@upmc.edu
Bill T
BT
Ameredes
Ruben
R
Zamora
Jigme M
JM
Sethi
He-Liang
HL
Liu
Lauryn K
LK
Kohut
Amber L
AL
Gligonic
Augustine M K
AM
Choi
William J
WJ
Calhoun
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D045853:Exhalation; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
D016207:Cytokines; D020382:Interleukin-18; D009573:Nitrites; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide