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Publication : Alterations in nitric oxide and cytokine production with airway inflammation in the absence of IL-10.

First Author  Ameredes BT Year  2005
Journal  J Immunol Volume  175
Issue  2 Pages  1206-13
PubMed ID  16002724 Mgi Jnum  J:100726
Mgi Id  MGI:3589345 Doi  10.4049/jimmunol.175.2.1206
Citation  Ameredes BT, et al. (2005) Alterations in nitric oxide and cytokine production with airway inflammation in the absence of IL-10. J Immunol 175(2):1206-13
abstractText  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.
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