{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:24:28Z","timestamp":1791188668160,"version":"4.1.0"},"reference-count":3,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron"],"published-print":{"date-parts":[[2000]]},"abstract":"<jats:p>&lt;i&gt;Background\/Aim:&lt;\/i&gt; In a previous study, we reported that interleukin (IL)-12 could upregulate the production of vascular permeability factor (VPF) derived from activated human peripheral blood mononuclear cells. Since IL-18, a novel immunoregulatory cytokine with potent interferon-\u03b3 inducing activities, has been shown to be a strong cofactor for T helper type 1 cell development, we tested the hypothesis that IL-18 in combination with IL-12 can act synergistically to modulate the production of VPF. &lt;i&gt;Methods:&lt;\/i&gt; For this purpose, T cells were isolated from heparinized venous blood, stimulated with concanavalin A, and incubated in the presence of IL-18 or IL-12, and the production of VPF was determined by the method of Lagrue. &lt;i&gt;Results:&lt;\/i&gt; There was a significant increase in VPF production from concanavalin A-stimulated T cells following incubation with IL-18 or IL-12. More importantly, the combination of the cytokines was found to give a potent synergistic stimulation of VPF by concanavalin A-activated T cells from normal subjects. To determine the specificity of the stimulatory effect, neutralizing anti-IL-18 and anti-IL-12 antibodies were preincubated with IL- 18 and IL-12, respectively, prior to the addition of responder cells. The antibodies completely inhibited the effects of IL-18 and IL-12. Thus, these data show that IL-18 can synergize with IL-12 to selectively increase the production of VPF from T cells. The present study further demonstrates that IL-18 and IL-12 are in fact acting in synergy in patients with minimal-change nephrotic syndrome. &lt;i&gt;Conclusions:&lt;\/i&gt; Taken together, our results indicate that both IL-18 and IL-12 contribute to the VPF production in vitro and suggest that they play key roles in the complexity of cytokine regulation in the pathophysiology of VPF.<\/jats:p>","DOI":"10.1159\/000045645","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T09:24:25Z","timestamp":1050398665000},"page":"127-133","source":"Crossref","is-referenced-by-count":27,"title":["Interleukin-18 and Interleukin-12 Synergize to Stimulate the Production of Vascular Permeability Factor by T Lymphocytes in Normal Subjects and in Patients with Minimal-Change Nephrotic Syndrome"],"prefix":"10.1159","volume":"85","author":[{"given":"Koichi","family":"Matsumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuo","family":"Kanmatsuse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2000,5,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000044968"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000013420"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"}],"container-title":["Nephron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/45645","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/45645","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:45:34Z","timestamp":1745469934000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000045645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000]]},"references-count":3,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2000,6,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000045645","archive":["Portico"],"relation":{},"ISSN":["1660-8151","2235-3186"],"issn-type":[{"value":"1660-8151","type":"print"},{"value":"2235-3186","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000]]}}}