DAB₃₈₉IL-2 recombinant fusion toxin effect on lymphocyte- and macrophage-producing cytokine subpopulation cells in experimentally induced demyelinating disease in mice

Abstract

Context We have reported previously that DAB389IL-2 recombinant fusion toxin targets IL-2R bearing CD4+ cells, and suppresses demyelinating disease in acute (A) - and chronic (C) - experimental autoimmune encephalomyelitis (EAE) animal models of multiple sclerosis. Objectives The present study was undertaken to investigate the effect of DAB389IL-2 treatment on various cytokine-secreting cell populations in A-EAE and C-EAE mice. Materials and methods The effects of DAB389IL-2 at doses of 200-, 800-, or 1600 kU administered i.v. on days 11–13 and 15 on the clinical score and cytokine-secreting cell populations were examined using flow cytometry. Results C-EAE mice treated with 1600 kU DAB389IL-2, but not A-EAE mice treated with 800 kU had significantly reduced disease. The CD3+CD25+ sub-population in spleens and spinal cords of A-EAE mice treated with 800 kU DAB389IL-2 was increased, whereas in C-EAE mice treated with 1600 kU this population was decreased. DAB389IL-2 treatment reduced CD3+CD4+, CD3+CD8+, CD4+CD8+, CD3+IL-2+, CD3+IFN-γ+ and CD3+TNF-α+ T cell subpopulations in the spinal cord in A-EAE, and C-EAE mice on day 16. CD11b+ macrophages that were IL-2-, IFN-γ-, and TNF-α-positive were reduced in A-EAE mice. DAB389IL-2 treatment reduced CD19+ B-cells positive for IL-2 or CD11b+ in the spinal cord in acute and chronic disease. DAB389IL-2 treatment also reduced lymph node CD3+CD8+, CD4+CD8+, CD3+CD25+ populations on day 16, and lymph node CD3+IL-10+ and peripheral blood CD3+CD25+ populations on day 24. Discussion and conclusions Our study demonstrates that DAB389IL-2 fusion toxin suppresses EAE in a dose-dependent manner, and alters inflammatory cell sub-populations during disease development.

Application of Cell-Based Therapies in Veterinary Dermatology

“…Later, cyclosporine was discovered to be efficient in psoriasis treatment by inhibiting cytokines produced by T cells [53]. Therefore, keratinocytes can trigger psoriasis and actively participate in a complex environment coordinated by cytokines [54]. The treatments depend on the severity of the disease, from topical agents and phototherapy to the usual immunosuppressant drugs [55].…”

Interleukin-2 Family Members and their Role in Demyelinating Disease

“…Adoptive transfers of myelin-specific CD4+ Th1 cells into naïve recipient mice promote the induction of EAE [13,14]. [17,18]. However, DAB 389 IL-2 also exhibit toxic side effect.…”