{"id":11744,"date":"2003-10-01T11:42:13","date_gmt":"2003-10-01T11:42:13","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=11744"},"modified":"2014-05-27T11:07:29","modified_gmt":"2014-05-27T11:07:29","slug":"il-2-induced-increases-in-cd4-counts-are-blunted-by-use-of-prednisone","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/11744","title":{"rendered":"IL-2 induced increases in CD4 counts are blunted by use of prednisone"},"content":{"rendered":"<p><strong>Simon Collins, HIV i-Base<\/strong><\/p>\n<p><strong>Early results from the large international ESPRIT study presented to the IAS conference this summer confirmed the ability of several courses of IL-2 to dramatically increase CD4 counts. However, IL-2 is associated with difficult side effects during the five-day administration periods including moderate to severe fatigue, myalgia and fever in up to 90% of subjects.<\/strong><\/p>\n<p>These symptoms are thought to be proinflammatory responses related to elevations in tumour-necrosis facto-alpha (TNF-alpha) and IL-6 that occur with IL-2 treatment. As corticosteroids inhibit production of TNF-alpha, a small pilot study looked at whether prednisone could reduce the side effects without reducing CD4 increases.<\/p>\n<p>Dr Jorge Tavel and colleagues from NIAID randomised 19 patients to one of four treatment groups (A-D): IL-2 + placebo (A), IL-2 + prednisone (B), prednisone alone (C) and placebo alone (D). Five patients were in each arm except the placebo arm, which had four patients. IL-2 was dosed at 7.5 MIU sc BID for each five day cycle, with cycles repeated every two months. Prednisone was dosed at 0.5mg\/kg\/day orally for seven days every two months, coinciding with the administration of IL-2.<\/p>\n<p>Increases in CD4 count were 452, 110, 27 and 135 in groups A, B, C and D respectively. All subjects in group A showed significant CD4 increases, but concomitant use of prednisone blunted or in some cases prevented this in subjects in group B.<\/p>\n<p>Although higher toxicity was reported in group A compared to B the researchers question whether these differences were significant. No difference in fatigue or dose reductions of IL-2 were reported between the groups A and B, although temperature was 0.4\u00b0C lower in those patients receiving prednisone.<\/p>\n<p>Although prednisone decreased levels of proinflammatory cytokines during IL-2 cycles, these responses appear to be critical to IL-2 induced CD4 increases.<\/p>\n<p>The authors conclude that IL-2 dose reduction in combination with use of nonsteroidal agents, is the best approach to manage toxicity and maximise response.<\/p>\n<p>Reference:<\/p>\n<p>Tavel JA, Sereti I, Walker RE et al. A randomised, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus. J Infect Dis. 2003 Aug 15;188(4):531-6.<br \/>\n<a href=\"http:\/\/www.ncbi.nlm.nih.gov:80\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=12898439&amp;dopt=Abstract\">http:\/\/www.ncbi.nlm.nih.gov:80\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=12898439&amp;dopt=Abstract<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Simon Collins, HIV i-Base Early results from the large international ESPRIT study presented to the IAS conference this summer confirmed the ability of several courses of IL-2 to dramatically increase CD4 counts. However, IL-2 is associated with difficult side effects &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-11744","post","type-post","status-publish","format-standard","hentry","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/11744","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=11744"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/11744\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=11744"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=11744"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=11744"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}