A Novel Method of Modifying Immune Responses by Vaccination with Lipiodol-siRNA Mixtures

Authors

Thomas E. Ichim, Medistem Laboratories Inc.
Igor A. Popov, University of Western Ontario
Neil H. Riordan, Medistem Laboratories Inc.
Hamid Izadi, Medistem Laboratories Inc.
Zaohui Zhong, The Second Xiangya Hospital of Central South University, Changsha, China
Li Yijian, The Second Xiangya Hospital of Central South University, Changsha, China
Salman Sher, Emory University
Eugenia K. Oleinik, Russian Academy of Sciences

Document Type

Article

Publication Date

1-3-2006

Journal

Journal of Translational Medicine

Volume

4

Issue

2

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-gamma 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.

Notes

Published in: Journal of Translational Medicine, 2006, 4:2. doi: 10.1186/1479-5876-4-2