CXCL11 and CCL2 are specific to HHV-6B in febrile infants

Japanese investigators from Kobe University identified CXC11 as a chemokine uniquely expressed in primary HHV-6B infections. They also confirmed a previous finding that cytokine CCL2 (MCP-1) plays a role in HHV-6B primary infections. Both CXCL11 and CCL2 are expressed in several neuroinflammatory conditions including epilepsy, Alzheimer’s disease, and traumatic brain injury.

Previous reports identified IL-2, IL-4, IL-5, IFN gamma, and CCL2/MCP-1 as elevated  in children with primary HHV-6B infections (Yoshikawa 2011). Several groups have also identified both IL-6 and TNF-alpha in the spinal fluid of infants with HHV-6B encephalopathy/encephalitis (Ichiyama 2009, Kawamura 2014). The Kobe group expanded the number of cytokines and chemokines examined to 40, and studied 233 infants with fever, including 30 with primary HHV-6B infections. They compared the inflammatory markers in this group to 25 infants who were ill but without fever.

Although other inflammatory markers are elevated in febrile infections, CXC11 and CCL2 appear to be uniquely elevated in infants with primary HHV-6B infection. CXCL10 and CDCL16 were also higher in patients with primary HHV-6B infection compared to afebrile patients, but were elevated in febrile patients with other infections as well.

IL-6, IL-8, and CCL2/MCP-1 have all been found to be elevated in the spinal fluid compared to the serum of patients with HHV-6B encephalopathy (Kawamura 2014). CCL2/MCP-1 is a potent chemoattractant for activated T cells and monocytes/macrophages. It has been implicated in the pathogenesis of atherosclerosis and is expressed in glial cells in epilepsy, brain injuries, and Alzheimer’s disease.

Gene expression of CXC11 and CXC10 is strongly induced by interferons, and CDC11 is chemotactic for activated T cells.

For more information, read the full paper (Nagasaka 2016).