Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-8-3
pubmed:abstractText
Acetaminophen (APAP) intoxication has been shown to activate Kupffer cells. Kupffer cell activation is also associated with the release of proinflammatory cytokines which can induce a variety of pathophysiological responses. These studies examined whether proinflammatory cytokines are produced in response to a hepatotoxic dose of APAP, and if so, the role they play in the observed pathological response. Female B6C3F1 mice received 500 mg APAP/kg in the presence and absence of antibodies against tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1 alpha), and IL-1 receptor antagonist (IL-1ra). Serum TNF-alpha, IL-1 alpha, and liver-associated enzyme levels were measured. In addition, the levels of mRNA transcripts for IL-1 alpha, IL-6, and TNF-alpha from livers of treated mice were examined by reverse transcription-polymerase chain reaction (RT-PCR). Administration of APAP resulted in an immediate reduction in body temperature as well as elevated serum levels of IL-1 alpha and TNF-alpha that reached a peak at 12 and 16 hr, respectively. The reduction in body temperature was partially blocked by injection of antibodies against TNF-alpha or IL-1 alpha. Furthermore, neutralization of TNF-alpha delayed the increase in serum IL-1 alpha and liver enzyme levels. In contrast, pretreatment with IL-1ra antisera exacerbated the effect of APAP on body temperature and increased the release of liver enzymes. These data suggest that TNF-alpha and IL-1 alpha are released in response to APAP intoxication and are responsible for certain pathological manifestations of APAP-induced hepatotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Role of proinflammatory cytokines in acetaminophen hepatotoxicity.
pubmed:affiliation
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
pubmed:publicationType
Journal Article