A novel method of modifying immune responses by vaccination with lipiodol-siRNA mixtures
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A novel method of modifying immune responses by vaccination with lipiodol-siRNA mixtures Thomas E Ichim*†1, Igor A Popov†2, Neil H Riordan1, Hamid Izadi1, Zaohui Zhong3, Li Yijian3, Salman Sher4 and Eugenia K Oleinik5 Address: 1Medistem Laboratories Inc, Tempe Arizona, USA, 2Department of Surgery, University of Western Ontario, London, Ontario, Canada, 3The Second Xiangya Hospital of Central South University, Changsha, China, 4Division of Cardiology, Emory University, Atlanta, USA and 5Institute of Biology, Karelian Research Center, Russian Academy of Sciences, Petrozavodsk, Russia Email: Thomas E Ichim* - [email protected]; Igor A Popov - [email protected]; Neil H Riordan - [email protected]; Hamid Izadi - [email protected]; Zaohui Zhong - [email protected]; Li Yijian - [email protected]; Salman Sher - [email protected]; Eugenia K Oleinik - [email protected] * Corresponding author †Equal contributors
Published: 03 January 2006 Journal of Translational Medicine 2006, 4:2
doi:10.1186/1479-5876-4-2
Received: 21 October 2005 Accepted: 03 January 2006
This article is available from: http://www.translational-medicine.com/content/4/1/2 © 2006 Ichim et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract The dendritic cell (DC) possesses the ability to stimulate both T helper 1 (Th1) and Th2 responses depending on activation stimuli. Although it is known that chemically or genetically modified DC can be used therapeutically to steer immune responses towards either Th1 or Th2, cellular therapy with ex vivo manipulated DC is clinically difficult. Here we demonstrate a novel method of switching immune responses from Th1 to Th2 through in vivo immune modulation by administration of siRNA. We demonstrate that siRNA targeting of the IL-12p35 gene leads to a Th2 bias in vitro through an IL-10 dependent mechanism. In vivo administration of siRNA admixed with the oil-based contrast agent lipiodol in the presence of antigen and adjuvant induced a deviation in recall response to reduced production of IFN-γ and augmented IL-4 response using either KLH or ovalbumin. This simple method of in vivo modification of immune response possesses therapeutic potential in Th1-mediated diseases such as multiple sclerosis and autoimmune diabetes.
Introduction It is known that the immune response can be polarized into two broad subsets based on cytokine secretion of the T helper cells. T helper-1 cells (Th1) responses are associated with anti-viral and anti-cancer immune reactions and are characterized by high secretion of the cytokine IFN-γ and IL-2 [1]. In contrast, Th2 responses are effective for clearing parasitic infections such as schistosoma mansoni and are identified by high secretion of IL-4 and IL-13 [2]. In various human
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