Macrophages transfected with adenovirus to express IL-4 reduce inflammation in experimental glomerulonephritis

D. C. Kluth, C. V. Ainslie, S. Finlay, Andrew Jackson Rees, W. P. Pearce, Daniel Clarke, I. Anegon

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    Abstract

    Nephrotoxic nephritis (NTN) is characterized by acute macrophage-dependent inflammation and serves as a model of human glomerulonephritis. In this study we have transfected rat macrophages with recombinant adenovirus expressing IL-4 (Ad-IL4) and demonstrated that these transfected macrophages develop fixed properties as a result of transfection, as shown by reduced NO production in response to IFN-gamma and TNF. Ad-IL4-transfected macrophages localized with enhanced efficiency to inflamed glomeruli after renal artery injection in rats with NTN compared with adenovirus expressing beta -galactosidase (Ad-beta gal)-transfected macrophages and produced elevated levels of the cytokine in glomeruli in vivo for up to 4 days. The delivery of IL-4-expressing macrophages produced a marked reduction in the severity of albuminuria (day 2 albuminuria, 61 +/- 15 mg/24 h) compared with unmodified NTN (day 2 albuminuria. 286 +/- 40 mg/24 h, p < 0.01), and this was matched by a reduction in the number of ED1-positive macrophages infiltrating the glomeruli. Interestingly, the injection of IL-4-expressing macrophages into single kidney produced a marked reduction in the numbers of EDI-positive macrophages in the contralateral noninjected kidney, an effect that could not be mimicked by systemic delivery of IL-4-expressing macrophages. This implies that the presence of IL-4-expressing macrophages in a single kidney can alter the systemic development of the inflammatory response. Macrophage transfection and delivery provide a valuable system to study and modulate inflammatory disease and highlight the feasibility of macrophage-based gene therapy.

    Original languageEnglish
    Pages (from-to)4728-4736
    Number of pages8
    JournalThe Journal of Immunology
    Volume166
    Issue number7
    Publication statusPublished - 2001

    Keywords

    • COLLAGEN-INDUCED ARTHRITIS
    • MEDIATED GENE-TRANSFER
    • DRAINING LYMPH-NODES
    • GLOMERULAR INJURY
    • HUMAN MONOCYTES
    • RAT-KIDNEY
    • IN-VIVO
    • LEUKOCYTE RECRUITMENT
    • CARTILAGE DESTRUCTION
    • ADHESION MOLECULE-1

    Cite this

    Kluth, D. C., Ainslie, C. V., Finlay, S., Rees, A. J., Pearce, W. P., Clarke, D., & Anegon, I. (2001). Macrophages transfected with adenovirus to express IL-4 reduce inflammation in experimental glomerulonephritis. The Journal of Immunology, 166(7), 4728-4736.