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Effects of acute systemic inhibition of nitric oxide synthase on plasma levels of pro‐and anti‐inflammatory cytokines in anesthetized mice
Author(s) -
Singh Purnima,
Castillo Alex,
Islam Mohammed T.,
Majid Dewan S. A.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1131.14
Subject(s) - nitric oxide synthase , nitric oxide , chemistry , oxidative stress , in vivo , cytokine , proinflammatory cytokine , pharmacology , endocrinology , superoxide , medicine , inflammation , biochemistry , enzyme , biology , microbiology and biotechnology
As demonstrated earlier that nitric oxide synthase (NOS) inhibition induced TNF‐α production both in‐vivo and in‐vitro, we examined further the hypothesis that NOS deficiency is primarily linked with induction of various inflammatory cytokines. Levels of pro‐(IL‐6 & MCP‐1) and anti‐inflammatory (IL‐10) cytokines were measured (using ELISA kits) in plasma collected from anesthetized mice (C57BL6; ~10 weeks age) infused with a NOS inhibitor, nitro‐L‐arginine methyl ester (L‐NAME; 200 μg/min/kg bw iv for 85 min; n=5). Compared to the values in vehicle treated mice (n=5), there were reductions in plasma levels of IL‐10 (2.5±0.7 vs 0.7±0.2 ng/mL), an increase in MCP‐1 (1.6±0.05 vs 3.1±0.4 ng/mL) without altering IL‐6 level (1.2 ± 0.1 vs 1.3±0.1 ng/mL) in L‐NAME treated mice. To assess the role for oxidative stress in these responses, L‐NAME was also infused in mice pre‐treated with a superoxide scavenger, tempol (2 μg/min/kg, iv; n=4). L‐NAME treatment in tempol pre‐treated mice also showed similar plasma IL‐6 (1.1±0.6 ng/mL) and IL‐10 (0.6±0.1 ng/mL) levels but lower MCP‐1 level (0.6±0.3 ng/mL). These data indicate that NOS inhibition induced production of pro‐inflammatory cytokine, MCP‐1 possibly via enhanced oxidative stress, but not affecting IL‐6 generation. These data also indicate that the production of anti‐inflammatory cytokine, IL‐10 is primarily linked to NOS activity. (Funded by NHLBI grant #66432)