Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-6-24
pubmed:abstractText
The local production of proinflammatory cytokines mediates the host response to inflammation, infection, and injury, whereas an overexpression of these mediators can injure or kill the host. Recently, we identified a class of multivalent guanylhydrazone compounds that are effective inhibitors of proinflammatory cytokine synthesis in monocytes/macrophages. The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection. Here, we addressed the hypothesis that spermine might counterregulate the innate immune response by downregulating the synthesis of potentially injurious cytokines. When spermine was added to cultures of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, MIP-1alpha, and MIP-1beta. The inhibition of cytokine synthesis was specific and reversible, with significant inhibition of TNF synthesis occurring even when spermine was added after LPS. The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity. Local administration of spermine in vivo protected mice against the development of acute footpad inflammation induced by carrageenan. These results identify a distinct molecular counterregulatory role for spermine in downregulating the monocyte proinflammatory cytokine response.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-1312903, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-14907970, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-1528880, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-1848573, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-1997652, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2115549, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2120285, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2163934, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2346594, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2495247, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2510929, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2537297, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2584936, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2643119, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2764054, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2783603, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-2838550, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3041283, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3226312, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3279154, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3317066, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3331368, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3754653, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3764421, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3977824, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-3980049, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-4112796, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-6468593, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7521253, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7523796, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7524490, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7569975, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7636207, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7689970, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7722463, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7843225, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7855252, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-7959870, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8075867, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8130014, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8253860, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8387893, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8426124, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8432617, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8455761, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8630372, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8632999, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-8642296, http://linkedlifedata.com/resource/pubmed/commentcorrection/9151701-938566
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
185
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1759-68
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
More...