Die Bedeutung der natürlichen Killerzell-Funktion bei Zytomegalievirus-seropositiven Patienten im Rahmen einer Sepsis
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Recent studies about sepsis show that cytomegalovirus (CMV) evidently acts as a pathogen co-factor. Several cytokines, like Tumor-necrose-factor alpha or Interferon gamma, are discussed to be mediators of CMV reactivation. It could be demonstrated that the partial immune deficiency in the context of sepsis can promote CMV-reactivation. The cytomegalovirus shows a high prevalence in the population. After primary infection an immunocompetent individual CMV displays a lifelong persisting infection in latency with periodical asymptomatic reactivation episodes, usually in the context of immunosuppression, for instance as an opportunistic infection in patients with AIDS. Natural killer (NK) cells are a member of the innate part of the immune system. They play an important role in the defense against intracellular pathogens, especially viruses and tumor cells. They have also regulatory and immunomodulatory functions. By releasing of cytokines they can influence other immune cells, for instance T cells. In a prospective study we investigated the role of NK cells in CMV reactivation in patients with sepsis and septic shock. The investigation was based on a newly established non-radioactive NK cell assay in our department according to the cytotoxic assay of Piriou et al. 2000. The previous gold standard in the assessment of the cytotoxic activity of NK cells and T cells was the 51Cr-release-assay, which served as a reference. In trials with several immunocompetent individuals we could show the reproducibility and validity of the NK assay based on FACS analysis. K562 cells susceptible to NK cell-mediated cytotoxicity worked as target cells. After preparing the NK cells of the patients by a Ficoll gradient the NK assay was performed and later on analysed by flow cytometry. In 38 patients participating in the study 17 patients were CMV-seropositive. We could demonstrate that all of the septic patients had CD16/56+-NK cells, but their NK cells showed no cytotoxic activity throughout the whole observation period except one single patient expressing temporary cytotoxic activity of the NK cells. In this patient we could demonstrate, that NK cell cytotoxicity can be suppressed by steroid application. About one third of the patients (32 %) displayed an active CMV infection with positive pp65 antigenemia within 14 days after inclusion in the study. Active CMV infection was self-limiting without application of antiviral therapy. CMV reactivation generally occurred despite intact CMV specific Th1-cell function. ICU treatment and need of mechanical ventilation was significantly prolonged (p < 0.05) in the group with active CMV infection. We conclude that proinflammatory immune responses in the line of sepsis may contribute to CMV reactivation. The adaptive T cell immunity more likely than NK cell immunity may contribute to the termination of active CMV infection without treatment with antiviral therapy.
Subject HeadingsCytomegalie-Virus [GND]
Natürliche Killerzelle [GND]
Septischer Schock [GND]
Killer cells [MeSH]