CXCL10

CXCL10 is a cytokine in the CXC chemokine family. C–X–C motif chemokine 10 (CXCL10) is also known as interferon γ-induced protein 10 kDa (IP-10) or small-inducible cytokine B10 is a cytokine. Through binding the CXCR3 receptor, CXCL10 induces chemotaxis, apoptosis, cell growth and angiostasis. Altered expression levels of CXCL10 have been associated with inflammatory diseases such as infectious disease, immune dysfunction and tumor development. CXCL10 is a biomarker that predicts severity of various diseases. Individuals infected with viruses, bacteria, fungi and parasites have been found to have abnormal levels of CXCL10 in their body fluids. It has been proposed that CXCL10 could be used as a therapeutic target for infectious diseases.

During inflammation CXCL10 is secreted in response to Interferon gamma (IFN-γ). CXCL10 is secreted from leukocytes, neutrophils, eosinophils, monocytes, epithelia, endothelial and stromal cells and keratinocytes during inflammation.

Depending on the host immune status and genetic background, CXCL10 may either protect or promote infection. CXCL10 has been reported to be protective in severe acute respiratory syndrome (SARS) induced by the coronavirus SARS-CoV. CXCL10 promotes facilitates infection by herpes simplex virus type 2 (HSV-2) and HIV by stimulating virus replication in macrophages and lymphocytes. Increased levels of CXCL10 occurs before the development of clinical symptoms for HIV infection, in the brain tissue of neonatal mice infected with polytropic murine retroviruses. SARS patients showed elevation of CXCL10 levels for at least two weeks after the onset of disease. Higher levels of CXCL10 are associated with failure of immunological treatment failure in HIV-infected patients following highly active anti-retroviral therapy (HAART) and pathogen burden and extent of organ damage in patients infected with both HIV and hepatitis C. A change in the genetic sequence in the promoter of the CXCL10 gene is a polymorphism correlates with susceptibility to chronic hepatitis B (HBV) infection. Treatments for infectious diseases including corticosteroid hormone for SARS, antiretroviral therapy or interference of CXCL10 and CXCR3 interactions for HIV reduce plasma CXCL10 levels.

CXCL10 (IP-10) was one of three cytokines, along with CCL7 and IL-1 receptor agonist, that showed continuously high levels in association with increased viral load, loss of lung function, lung injury and fatal outcome in COVID-19 patients. A clinical stage monoclonal antibody targeting CXCL10 is being developed along with an antibody targeting toll-like receptor 4 (TLR4) for the treatment of an exaggerated immune response associated with some cases of COVID-19 where patients can progress to the life threatening conditions, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Edesa Biotech has an exclusive licensing agreement from Light Chain Bioscience to develop the two therapies. High levels are CXCL10 are found in patients with ARDS and experiments using animal models have shown that lowering levels of CXCL10 decreases severity of ARDS and ALI.