Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.

TLDR

The outcome of an immune response is best predicted by the lymphokine phenotype of responding T cells, with Th1 cytokines driving delayed type hypersensitivity and inflammation and Th2 cytokines promoting antibody production. The study aimed to test whether inducing Th2‑like cells with interleukin‑4 would modulate the inflammatory response in experimental allergic encephalomyelitis. IL‑4 was administered to mice with EAE, a Th1‑mediated autoimmune disease targeting myelin basic protein, to induce Th2‑like cells. IL‑4 treatment ameliorated clinical disease, induced MBP‑specific Th2 cells, reduced demyelination, and suppressed inflammatory cytokine synthesis in the CNS, indicating that shifting from Th1‑dominant to Th2‑dominant responses may have therapeutic potential for autoimmune diseases.

Abstract

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.