title: Human cytomegalovirus induces systemic immune activation characterized by a type 1 cytokine signature.
abstract: Mechanisms underlying the onset and perpetuation of chronic immune activation in individuals without overt infectious or autoimmune diseases are unclear. Cytomegalovirus (CMV) is a persistent virus that induces a permanent increase of highly differentiated, interferon-gamma-secreting effector T cells. We hypothesized that, because of this increase, CMV also induces a systemic inflammatory response. We measured acute phase proteins, cytokines, and chemokines in serum samples from renal transplant recipients who developed a primary CMV infection and healthy CMV serum-positive or -negative individuals. Primary CMV infection induced a clear proinflammatory response that was maintained during latency. This response was characterized by increased levels of acute phase proteins, such as serum amyloid-A and C-reactive protein, and type 1 cytokines, such as interleukin-18, interferon-inducible protein-10, and interferon-gamma. This continuous activation of the immune system may play a role in the pathogenesis of chronic allograft rejection and potentially contribute to the acceleration of chronic diseases.
authors.affiliation: Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. p.j.vandeberg@amc.nl
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: van de Berg
authors.forename: Kirstin M
authors.initials: KM
authors.lastname: Heutinck
authors.forename: Robin
authors.initials: R
authors.lastname: Raabe
authors.forename: Robert C
authors.initials: RC
authors.lastname: Minnee
authors.forename: Si La
authors.initials: SL
authors.lastname: Young
authors.forename: Karlijn A
authors.initials: KA
authors.lastname: van Donselaar-van der Pant
authors.forename: Frederike J
authors.initials: FJ
authors.lastname: Bemelman
authors.forename: Rene A
authors.initials: RA
authors.lastname: van Lier
authors.forename: Ineke J
authors.initials: IJ
authors.lastname: ten Berge
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D017735:Virus Latency
chemical_list: D016207:Cytokines; D020382:Interleukin-18; D007371:Interferon-gamma; D002097:C-Reactive Protein