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.
Ameredes
Bill T
BT
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
Zamora
Ruben
R
Sethi
Jigme M
JM
Liu
He-Liang
HL
Kohut
Lauryn K
LK
Gligonic
Amber L
AL
Choi
Augustine M K
AM
Calhoun
William J
WJ
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