Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transfer

J Immunol. 1998 Aug 1;161(3):1516-24.

Abstract

Autoimmune arthritides are characterized by an imbalance between pro- and anti-inflammatory cytokines. Viral IL-10 (vIL-10) shares many of the anti-inflammatory properties of mouse and human IL-10, but lacks their immunostimulatory properties and may therefore offer superior immunosuppression. Viral IL-10 has a short half-life; however, genetic modification of cells in vivo offers a potential means of achieving prolonged therapeutic titers. To determine the effects on collagen-induced arthritis of vIL-10 gene transfer, DBA/1 mice were administered i.v. or intra-articular injections of Av(vIL-10), a replication-deficient adenovirus encoding vIL-10. The i.v. injection of Av(vIL-10) before disease onset delayed the onset and reduced the severity of collagen-induced arthritis, but treatment of established disease was ineffective. The preventative effects were not due to decreased anti-type II collagen Ab production. Rather, T cells from mice treated with Av(vIL-10) demonstrated a decreased in vitro proliferative response to type II collagen, and a delay was observed in up-regulation of synovial mRNA for the proinflammatory cytokines IL-2 and IL-1beta. Intra-articular injection of Av(vIL-10) into knee joints did not reduce arthritis in the knees, but inhibited the development of arthritis in the paws. Humoral and cellular immune responses against Av(vIL-10) were observed. These results demonstrate that vIL-10 can significantly alter the course of autoimmune arthritis and emphasize the complexities of using gene transfer as a method of drug delivery for arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Arthritis, Experimental / epidemiology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Collagen / immunology*
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Freund's Adjuvant
  • Gene Transfer Techniques*
  • Genetic Vectors / administration & dosage*
  • Immunoglobulin G / biosynthesis
  • Incidence
  • Injections, Intra-Articular
  • Injections, Intravenous
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics*
  • Knee Joint / pathology
  • Lymphocyte Activation / genetics
  • Male
  • Mice
  • Mice, Inbred DBA
  • RNA, Messenger / biosynthesis
  • Time Factors

Substances

  • Cytokines
  • Immunoglobulin G
  • RNA, Messenger
  • Interleukin-10
  • Collagen
  • Freund's Adjuvant