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Independent suppression of nitric oxide and TNFα in the lung of conscious rats by ethanol 1
Author(s) -
Xie Jianming,
Kolls Jay,
Bagby Greg,
Greenberg Stan S.
Publication year - 1995
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.9.2.7540157
Subject(s) - bronchoalveolar lavage , tumor necrosis factor alpha , chemistry , nitric oxide synthase , nitric oxide , lipopolysaccharide , messenger rna , microbiology and biotechnology , endocrinology , medicine , ethanol , polyclonal antibodies , lung , immunology , biochemistry , antibody , biology , gene , organic chemistry
Tumor necrosis factor‐α (TNFα) and nitric oxide (NO) mediate in part the microbicidal response of murine and rodent alveolar macrophages (AM) and recruited neutrophils (PMN) to airborne infections. Ethanol (ETOH) suppresses intrapulmonary TNFα and NO release and impairs pulmonary host defense mechanisms. We tested the concept that ETOH down‐regulates NO by inhibiting production of TNFα. Male rats were given intratracheal (i.t.) saline (PBS), a polyclonal anti‐TNFα antibody (TNFab) or nonimmune IgG (22 mg/kg, i.m.) 2 h before giving i.t. Escherichia coli endotoxin (LPS) to normal rats or rats pretreated with ETOH (5.5 g/kg, i.p.) 30 min before experimentation. AM and PMN were obtained from the bronchoalveolar lavage fluid (BAL) fluid of rats killed 2 and 4 h after administration of LPS. mRNA for inducible NO synthase (iNOS) and TNFα were measured in AM and PMN with competitor equalized RT‐PCR techniques. The BAL fluid, AM, and PMN were assayed for TNFα and NO 2 – , and NO 3 – (RNI) with the L929 bioassay and chemiluminescence, respectively. TNFab abolished LPS‐induced increases in TNFα but did not suppress the NO content of the BAL fluid or gene expression for iNOS by AM or PMN. ETOH suppressed LPS‐induced increases in mRNA for iNOS, production of RNI, and BAL fluid TNFα but did not affect LPS‐induced increases in mRNA for TNFα. ETOH‐induced attenuation of LPS‐induced up‐regulation of the iNOS system did not differ in rats pretreated with TNFab or IgG. Thus, ETOH down‐regulates iNOS gene expression and RNI production independent of its effects on TNFα. Acute ETOH administration suppresses iNOS at the level of transcription and TNFα at the level of translation or release of the peptide.—Xie, J., Kolls, J. K., Bagby, G., Greenberg, S. S. Independent suppression of nitric oxide and TNFα in the lung of conscious rats by ethanol. FASEB J. 9, 253–261 (1995)