Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-1-4
pubmed:abstractText
In search of an optimized anti-cancer immunotherapy, the combination of IL-2 and IL-1 has been tried. In an in-vitro LAK model, this cytokine cocktail seemed to be quite promising. In our in-vitro model of IL-2 induced T-cell activation we have therefore investigated the co-operation of these two potent immunostimulators. Mononuclear cells were stimulated with CD3 activating antibody in the presence of different cytokines and blocking or neutralizing antibodies. Cytokine concentrations were detected in the supernatants with ELISA. Intracellular IFN-gamma and IL-4 in the different T-cell subsets was measured by flow cytometry. IL-1 and IL-1 receptor antagonist (IL-1Ra) were up-regulated by IL-2, this was achieved independently of IL-12 or CD40/CD40L interaction. As a negative feedback mechanism, IL-1beta induced its natural antagonist, IL-1Ra. Both endogenous and exogenous IL-10 suppressed IL-1beta and induced IL-1Ra, thus markedly decreased the amount of functional IL-1. The combination of IL-2 and IL-1beta lead to a mildly increased Interferon-gamma (IFN-gamma) secretion (+20%, p < 0.05), however, this appeared to be the result of an increased IFN-gamma production per secreting cell, rather than of an increased recruitment of non-secreting cells. Similarly, IL-6 was also induced in an additive fashion (+30%, p < 0.05). For both cytokines, this effect could be significantly augmented by neutralizing IL-1Ra. Concentrations of IL-2 induced IL-10 and soluble Fas ligand (sFasL) were not affected by IL-1beta. We were thus able to demonstrate that IL-1 relays its activity through different pathways than IL-2. Furthermore, we could show that the potentially synergistic action of IL-2 and IL-1 was hindered by the simultaneous induction of signficant amounts of IL-1Ra. From the latter findings we conclude that the combination of IL-2 and IL-1 for cytokine-induced anti-tumor activity may not, but a combination of IL-2 and anti-IL-1Ra might prove beneficial.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand, http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein, http://linkedlifedata.com/resource/pubmed/chemical/IL1RN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin 1 Receptor Antagonist..., http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0882-0139
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-302
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11777281-CD40 Ligand, pubmed-meshheading:11777281-Cell Differentiation, pubmed-meshheading:11777281-Cells, Cultured, pubmed-meshheading:11777281-Fas Ligand Protein, pubmed-meshheading:11777281-Humans, pubmed-meshheading:11777281-Interferon-gamma, pubmed-meshheading:11777281-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:11777281-Interleukin-1, pubmed-meshheading:11777281-Interleukin-10, pubmed-meshheading:11777281-Interleukin-12, pubmed-meshheading:11777281-Interleukin-2, pubmed-meshheading:11777281-Interleukin-6, pubmed-meshheading:11777281-Leukocytes, Mononuclear, pubmed-meshheading:11777281-Lymphocyte Activation, pubmed-meshheading:11777281-Membrane Glycoproteins, pubmed-meshheading:11777281-Sialoglycoproteins, pubmed-meshheading:11777281-Signal Transduction, pubmed-meshheading:11777281-T-Lymphocytes
pubmed:year
2001
pubmed:articleTitle
Co-operation of IL-1 and IL-2 on T-cell activation in mononuclear cell cultures.
pubmed:affiliation
Heinrich-Heine University, Center of Child Health, Department of Pediatric Hematology and Oncology, Düsseldorf, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't