title: Interleukin 13 suppresses cytokine production and stimulates the production of 15-HETE in PBMC. A comparison between IL-4 and IL-13.
abstract: We examined the ability of rIL-13 to regulate rIL-l alpha induced IL-1 beta, IL-1 receptor antagonist (IL-1ra) and IL-8 production in cultured peripheral blood mononuclear cells (PBMC), endothelial cells and fibroblasts. Furthermore we examined whether rIL-13 could influence the production of the arachidonic acid products LTB4, 12-HETE and 15-HETE by PBMC. rIL-1 alpha-stimulated PBMC cultures secreted high levels of IL-1 beta and IL-8; this could be inhibited to the level of unstimulated control cells by co-incubation with rIL-13 (10 ng/ml). IL-13 induced a 3-fold increase of the IL-1ra secretion which was inhibited by rIFN-gamma. In the presence of both rIL-1 alpha and rIL-13, endothelial cells increased IL-8 secretion, whereas dermal fibroblasts remained unchanged. Of the arachidonic acid metabolites examined, the greatest change was observed in the formation of 15-HETE. In unstimulated PBMC cultures the amount of 15-HETE was less than 4 ng/10(6) cells, whereas after addition of rIL-13 we measured a formation of 139 +/- 6.2 ng/10(6) cells. The effect of rIL-13 on the 15-HETE formation in PBMC was abolished by addition of 100 U/ml rIFN-gamma. rIL-13 only induced minor changes in the LTB4 and 12-HETE formation. Compared to IL-4, IL-13 induced a similar alteration of the cytokine cascade and arachidonic acid metabolism, supporting the hypothesis that the two cytokines use a common receptor complex or signal pathway.
authors.affiliation: Department of Rheumatology, University Hospital of Aarhus, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Deleuran
authors.forename: L
authors.initials: L
authors.lastname: Iversen
authors.forename: M
authors.initials: M
authors.lastname: Deleuran
authors.forename: H
authors.initials: H
authors.lastname: Yssel
authors.forename: K
authors.initials: K
authors.lastname: Kragballe
authors.forename: K
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: K
authors.initials: K
authors.lastname: Thestrup-Pedersen
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D007975:Leukotriene B4 / Q000096:biosynthesis; D051379:Mice; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D006893:Hydroxyeicosatetraenoic Acids; C508181:IL13RA1 protein, human; C507763:IL1RN protein, human; C508183:Il13ra1 protein, mouse; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D016209:Interleukin-8; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D007975:Leukotriene B4; D015847:Interleukin-4; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D007371:Interferon-gamma