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The role of IL‐6 in the inflammatory and humoral response to adenoviral vectors
Author(s) -
Benihoud Karim,
Salone Barbara,
Esselin Stephanie,
Opolon Paule,
Poli Valeria,
Di Giovine Monica,
Perricaudet Michel,
Saggio Isabella
Publication year - 2000
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/(sici)1521-2254(200005/06)2:3<194::aid-jgm102>3.0.co;2-5
Subject(s) - immune system , biology , transgene , adenoviridae , tumor necrosis factor alpha , immunology , genetic enhancement , viral vector , inflammation , acute phase protein , recombinant dna , virology , gene , genetics
Background The major concern for the use of adenoviral vectors for gene therapy is the viral‐induced immune response that has been shown to be responsible for short‐term transgene expression and inefficient viral readministration. In vivo studies and clinical trials with recombinant adenovirus have suggested a role for interleukin 6 (IL‐6) in the inflammatory reaction that follows Ad‐infection. IL‐6 plays an important role in the acute‐phase innate response, in the differentiation of B‐cells and in the activation of the Th2 cell subsets. Methods To clarify the role of IL‐6 in the immune response to Ad‐vectors, we used IL‐6 knock‐out mice (IL‐6 −/− ). E1/E3 deleted recombinant adenoviruses encoding reporter genes were administered to wild type or IL‐6 −/− mice; transgene expression kinetics and immune response were analyzed. Results Acute phase protein production was significantly diminished in IL‐6 −/− mice after adenoviral injection. No significant difference between wild type and knock‐out animals in the level or the nature of leucocyte recruitment in the liver was detectable. A minor decrease in the IgG response to Ad‐recombinants was observed in knock‐out mice. Gene transfer efficiency, both in terms of levels and duration of transgene expression, were comparable in IL‐6 +/+ and IL‐6 −/− mice. An increase in IL‐1β and tumor necrosis factor‐α (TNF‐α) levels was observed in the sera of IL‐6 −/− mice as compared to wild type animals: this phenomenon represents a possible compensatory mechanism for the establishment of the immune phenotype observed in mutant mice. Conclusions IL‐6 plays a role in the acute phase response to adenoviral vectors. Nevertheless, possibly due to a compensatory mechanism exerted by other cytokines, the antibody and cellular responses to adenoviruses are very similar in wild type and IL‐6 −/− mice. Copyright © 2000 John Wiley & Sons, Ltd.