Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-11-15
pubmed:abstractText
Pentoxifylline (PTX), a methylxanthine derivative, has been reported to be an effective drug in inhibiting TNF-alpha responses during septic shock. The inhibition of TNF-alpha production seems to be correlated with increased intracellular cAMP levels. PTX also affects the production of other cytokines such as IL-1, IL-6, IL-10, IL-12, and IFN-gamma. However, inhibition, as well as enhancement of cytokine production, has been observed in vitro, depending on the PTX concentration and cell type used.IL-12 is a heterodimeric cytokine that plays an important role in the development of Th1-mediated inflammatory responses. IL-12 along with TNF-alpha and other proinflammatory cytokines has shown to be responsible for the pathological reaction, which may lead to septic shock. For biological activity, the expression of both subunits of IL-12, p35 and p40, is required. Moreover, the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In this study, we investigated the effects of PTX on the production of both proinflammatory (TNF-alpha, IL-6, IL-12) and anti-inflammatory (IL-10) cytokines by murine macrophages (Mφ). We have found that PTX, at concentrations below 100 microg/ml, selectively inhibited the production of TNF-alpha. Forskolin, a cAMP-elevating agent, similarly affected the production of the cytokines tested. However, at higher concentrations, PTX inhibited the production of TNF-alpha, IL-10, and IL-12 p35, but surprisingly, PTX enhanced the production of IL-12 p40. Concentrations of IL-10 were negatively correlated with the concentrations of IL-12 p40 subunit. These results further confirm the relevance of the use of PTX in clinical trials of immunological disorders characterised by inappropriate Th1 type immune responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0162-3109
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-43
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:10996031-Animals, pubmed-meshheading:10996031-Cells, Cultured, pubmed-meshheading:10996031-Cricetinae, pubmed-meshheading:10996031-Cyclic AMP, pubmed-meshheading:10996031-Cytokines, pubmed-meshheading:10996031-Drug Combinations, pubmed-meshheading:10996031-Forskolin, pubmed-meshheading:10996031-Interferon-gamma, pubmed-meshheading:10996031-Interleukin-10, pubmed-meshheading:10996031-Interleukin-12, pubmed-meshheading:10996031-Lipopolysaccharides, pubmed-meshheading:10996031-Macrophages, Peritoneal, pubmed-meshheading:10996031-Male, pubmed-meshheading:10996031-Mice, pubmed-meshheading:10996031-Mice, Inbred DBA, pubmed-meshheading:10996031-Pentoxifylline, pubmed-meshheading:10996031-Phosphodiesterase Inhibitors, pubmed-meshheading:10996031-Rats, pubmed-meshheading:10996031-Th1 Cells, pubmed-meshheading:10996031-Th2 Cells
pubmed:year
2000
pubmed:articleTitle
Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages.
pubmed:affiliation
Department of Immunology, Jagiellonian University Medical College, 18 Czysta Street, 31-121, Cracow, Poland. mmmarcin@cyf-edu.kr-pl
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't