Title:Application of Agents Against Interferon-Gamma-Dependent Chemokines in Immunotherapy
Volume: 12
Issue: 9
Author(s): Poupak Fallahi, Silvia Martina Ferrari, Dilia Giuggioli, Clodoveo Ferri and Alessandro Antonelli
Affiliation:
Keywords:
CXCR3 chemokines, autoimmune thyroiditis, graves’ disease and ophthalmopathy, inflammatory myopathies,
rheumatoid arthritis, type 1 diabetes.
Abstract: The C-X-C chemokine receptor (CXCR)3 and its chemokines (CXCL9, CXCL10,
CXCL11) are involved in the pathogenesis of autoimmune disesases. Under the influence of interferon(
IFN)γ, the IFNγ-inducible chemokines are secreted by lymphocytes, and by target cells (fibroblasts,
epithelial cells, etc). In target tissues, Th1 lymphocytes are recruited; hence IFNγ is enhanced,
which stimulates IFNγ-inducible chemokines (CXCL9, CXCL10, CXCL11) secretion reiterating the
autoimmune process.
Many studies have evaluated if blockade of CXCR3 or its chemokines have therapeutic significance in autoimmune diseases
(for example in thyroid autoimmune disorders, etc).
Peroxisome proliferator-activated receptor (PPAR)γ or -α agonists show a strong inhibitory effect on the expression and
production of CXCR3 chemokines in vitro, in various kinds of cells, such as denditric cells, monocytes, macrophages, endothelial
and vascular smooth muscle cells, intestinal cells, thyrocytes, fibroblasts, preadipocytes and mesangial cells, and
in vivo in animal models.
Further studies are ongoing to explore the use of new molecules that act as antagonists of CXCR3, or block CXCL10, in
autoimmune disorders, and many interesting patents have been recently applied. Phase II studies have assessed the efficacy
and safety of fully human, monoclonal antibodies to CXCL10, for the treatment of autoimmune disorders (for example
rheumatoid arthritis, or ulcerative colitis).
