Galectin-1 (GAL-1), a member of a family of conserved β-galactoside–binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2–polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1–expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an Aq-restricted, collagen type 2–specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1–mediated autoimmune disorders.

Objective. To investigate the therapeutic effects and possible mechanisms of action of constitutive expression of interferon-␤ (IFN␤) by syngeneic fibroblasts from DBA/1 mice in the collagen-induced arthritis (CIA) model.Methods. Immortalized embryonic DBA/1 fibroblasts were infected with a retrovirus expressing murine IFN␤. IFN␤-expressing fibroblasts were then implanted intraperitoneally into mice immunized with bovine type II collagen. The effect of IFN␤ on paw swelling, anticollagen antibody levels, IgG1/IgG2a isotype profiles, arthritis score, histologic joint damage, and cytokine secretion from lymph node cells and from bone marrowderived macrophages was assessed.Results. A single injection of IFN␤-secreting fibroblasts was sufficient to prevent arthritis or to ameliorate existing disease. Thus, IFN␤ reduced the clinical score and paw swelling irrespective of whether the injection was administered before or after disease onset in treated mice, compared with that in the untreated control group (P < 0.05). Histologic findings in the IFN␤-treated mice were markedly less severe than in the control group (P < 0.001). This effect was accompanied by a decrease in total anticollagen IgG levels, a decrease in anticollagen IgG2a, and an increase in IgG1. In vitro, supernatants from these engineered fibroblasts inhibited collagen-induced interferon-␥ secretion from lymph node cells, and reduced the levels of tumor necrosis factor ␣ and interleukin-12 produced by lipopolysaccharide/IFN␥-treated bone marrow-derived macrophages. This effect was specific, since it was reversed with anti-IFN␤ polyclonal antibodies.Conclusion. These results indicate that IFN␤, which is currently used as a treatment for relapsing, remitting multiple sclerosis, is a potent immunomodulatory and antiinflammatory cytokine in CIA and should be considered for the treatment of rheumatoid arthritis.Interferons are known predominantly for their inhibitory effects on viral replication and cellular proliferation, as well as for their capacity to modulate immune responsiveness. Interferon-␥ (IFN␥), for example, plays an important role in promoting immune and inflammatory responses, partly by up-regulating the antigenpresenting capacity of different cell types and partly by priming macrophages for proinflammatory cytokine production. In contrast, there is evidence of a predominantly antiinflammatory role for interferon-␤ (IFN␤), a type I interferon. This evidence is based principally on the beneficial therapeutic effect of IFN␤ in patients with multiple sclerosis (MS) (1) as well as in chronic, relapsing experimental allergic encephalomyelitis (an animal model of MS) (2,3). Specifically, administration of IFN␤ to MS patients in clinical trials has been shown to reduce the level of disease activity and the frequency of attacks (4). Conversely, the administration of IFN␥ is associated with exacerbation of preexisting autoimmune diseases such as systemic lupus erythematosus and MS (5,6). These findings support the concept that IFN␤ and IFN␥ have opposing e...