High Incidence of Active Cytomegalovirus Infection Among Septic Patients

Abstract

Cytomegalovirus (CMV) infection is an important cause of disease in immunocompromised patients. In a prospective longitudinal study of 34 septic patients, the incidence of active CMV infection was examined. Eleven of 34 patients (32.4%) had active CMV infection, diagnosed by immunocytochemical staining of CMV pp65 antigen in blood leukocytes and/or detection of CMV DNA by PCR. Positive results for CMV infection were obtained in a median of 4 days (by PCR) or 11 days (by staining of pp65 antigen) after onset of sepsis. Twenty patients for whom more than one sample was examined were selected for further analysis. Among the patients with active CMV infection (nine of 20) there was a trend toward higher median values of tumor necrosis factor a, interleukin1b, alanine aminotransferase, and aspartate aminotransferase in plasma, in comparison with the values for patients without CMV infection. Sepsis in patients with CMV infection may affect outcome of the disease. Cytomegalovirus (CMV) is an important cause of morbiditySee the editorial response by Ho on pages 1083 -4. and death in immunocompromised patients, such as those with AIDS or immunosuppressed transplant recipients [1, 2]. After Furthermore, it has been hypothesized that TNF-a is of some primary infection, which usually takes place during childhood, importance in activation of CMV and HIV replication and CMV (as with all herpesviruses) resides in the host throughout immunopathology in in vitro experiments or during in vivo life; therefore, 50% -100% of the population -depending on circumstances [11 -15]. In 1994 results of a study were pubcountry of residence and social status -have become CMVlished supporting the hypothesis that TNF-a influences CMV seropositive by adulthood [3]. Disturbance of the fine balance reactivation, and clinical observation in septic patients seemed between the immune system and the latently existing virus by to confirm this hypothesis [16]. The aim of the present longituimmunosuppressive therapy, HIV infection, or another form of dinal prospective study was to define the incidence of CMV immunosuppression results in viral reactivation and clinical reactivation in patients with sepsis and to investigate the reladisease.tionship between severity of disease, cytokine concentration in Severe dysregulation of central mediators of the immune plasma, and clinical outcome. system, as occurs during sepsis, may induce such a state of immunosuppression. Sepsis is defined as a systemic inflammatory response that results from infection [4]. It is increasingly Patients and Methods common and was shown to be associated with a mortality ranging from Ç20% to 30%, up to 56% in controlled clinical Inclusion Criteria and Definitions trials [5 -8]. TNF-a, IL-1, and IL-6 were shown to represent As no uniform definition of sepsis has been generally acimportant factors in the pathogenesis of sepsis [9]. Despite cepted, the definition of sepsis used in this study followed the their physiological benefits for the host, they may also cause criteria of the Am...

Transplant-induced reactivation of murine cytomegalovirus immediate early gene expression is associated with recruitment of NF-κB and AP-1 to the major immediate early promoter

“…Allograft rejection, sepsis, acute illness, IL-6 and TNF have long been implicated in reactivation of HCMV in patients (Cook et al, 1998;Döcke et al, 1994;Fietze et al, 1994;Grattan et al, 1989;Heininger et al, 2001;Hibberd et al, 1992;Kalil & Florescu, 2009;Kutza et al, 1998;Lao et al, 1997;Limaye et al, 2008;Mutimer et al, 1997;Portela et al, 1995;Razonable et al, 2001;Reinke et al, 1994a) and allogeneic stimulation, TNF, IL-6 and lipopolysaccharide have been shown to induce reactivation of HCMV in experimental models (Hargett & Shenk, 2010;Huang et al, 2012;Kew et al, 2014;O'Connor & Murphy, 2012;Reeves & Compton, 2011;Söderberg-Nauclér et al, 1997). Allogeneic transplantation and TNF are sufficient to activate both an HCMV MIEP-lacZ transgene and MCMV IE gene expression (Hummel et al, 2001).…”

“…Thus, a greater understanding of the molecular events controlling reactivation from latency is needed to develop alternative strategies to prevent CMV disease. Döcke et al, 1994;Fietze et al, 1994;Grattan et al, 1989;Heininger et al, 2001;Hibberd et al, 1992;Kalil & Florescu, 2009;Kutza et al, 1998;Lao et al, 1997;Limaye et al, 2008;Mutimer et al, 1997;Portela et al, 1995;Razonable et al, 2001;Reinke et al, 1994aReinke et al, , 1994b) and the inflammatory cytokine TNF has been proposed to drive reactivation through NF-k B-mediated activation of the major immediate early promoter (MIEP) (Döcke et al, 1994;Fietze et al, 1994;Prösch et al, 1995;Stein et al, 1993). However, due to the species specificity of HCMV, it has not been possible to test this hypothesis in the context of organ transplantation.…”

Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

“…CMV has been shown to suppress T cells, NK cells, macrophages, neutrophils and dendritic cells 38,[43][44][45] and is clinically associated with death in cases of bacterial and fungal infection. 32,38,46 It was somewhat surprising, however, that the impact of a CMV infection lasts for such a long time after HSCT. Although several patients experienced repeated reactivation during the early phase after HSCT, we did not routinely monitor CMV for longer than 6 months after HSCT, so we do not know if the patients experienced repeated and/or prolonged CMV reactivation contributing to the long-term risk of fatal infections.…”

HCMV-Encoded UL128 Enhances TNF-α and IL-6 Expression and Promotes PBMC Proliferation Through the MAPK/ERK PathwayIn Vitro

“…CMV infection increases the expression of cytokines such as TNF-a, IL-6, and IL-8 (17,18). Observations of clinical samples showed that the increased serum levels of TNF-a seen in patients with sepsis and atopic dermatitis were related to activation of latent HCMV (19,20). Expression of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in HCMV-mediated angiogenesis, and may contribute to the development of HCMV-associated vascular diseases (21).…”