Dataset Information

Aged mice are unable to mount an effective myeloid response to sepsis.

ABSTRACT: The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6-12 wk) or aged (20-24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with young mice. No differences were found in the magnitude of the plasma cytokine responses. Although septic aged mice displayed equivalent or increased numbers of circulating, splenic, and bone marrow myeloid cells, some of these cells exhibited decreased phagocytosis, reactive oxygen species production, and chemotaxis. Blood leukocyte gene expression was less altered in aged versus young mice 1 d after sepsis. Aged mice had a relative inability to upregulate gene expression of pathways related to neutrophil-mediated protective immunity, chemokine/chemokine receptor binding, and responses to exogenous molecules. Expression of most MHC genes remained more downregulated in aged mice at day 3. Despite their increased myeloid response to sepsis, the increased susceptibility of aged mice to sepsis appears not to be due to an exaggerated inflammatory response, but rather, a failure to mount an effective innate immune response.

SUBMITTER: Nacionales DC

PROVIDER: S-EPMC3884685 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aged mice are unable to mount an effective myeloid response to sepsis.

Nacionales Dina C DC Gentile Lori F LF Vanzant Erin E Lopez M Cecilia MC Cuenca Angela A Cuenca Alex G AG Ungaro Ricardo R Li Yi Y Baslanti Tezcan Ozrazgat TO Bihorac Azra A Moore Frederick A FA Baker Henry V HV Leeuwenburgh Christiaan C Moldawer Lyle L LL Efron Philip A PA

Journal of immunology (Baltimore, Md. : 1950) 20131213 2

The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6-12 wk) or aged (20-24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with young mice. No differences were found in the magnitude of ...[more]

PMID: 24337739

Similar Datasets

Project description:BackgroundDespite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60?-?70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice.MethodsMale C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that of the elderly). Mice were prevented from becoming obese by food restriction (given 70-90% of ad libitum consumption amount). Between 20 and 22 months, a subgroup of mice ran voluntarily on wheels, alternating 1-3 days of running with 1-2 days of rest. At 22 months, mice were intraperitoneally injected with sterile saline (control) or 3.75 g/kg fecal slurry (septic). At 7 h post injection, we examined (1) neutrophil influx in the lung and liver by measuring myeloperoxidase and/or neutrophil elastase in the tissue homogenates by spectrophotometry, (2) interleukin 6 (IL6) and KC in the lung lavage by ELISA, (3) pulmonary surfactant function by measuring percentage of large aggregates, (4) capillary plugging (pro-coagulant response) in skeletal muscle by intravital microscopy, (5) endothelial nitric oxide synthase (eNOS) protein in skeletal muscle (eNOS-derived NO is putative inhibitor of capillary plugging) by immunoblotting, and (6) systemic blood platelet counts by hemocytometry.ResultsSepsis caused high levels of pulmonary myeloperoxidase, elastase, IL6, KC, liver myeloperoxidase, and capillary plugging. Sepsis also caused low levels of surfactant function and platelet counts. Running exercise increased eNOS protein and attenuated the septic responses.ConclusionsVoluntary running protects against exacerbated sepsis-induced inflammatory and pro-coagulant responses in aged mice. Protection against pro-coagulant responses may involve eNOS upregulation. The present discovery in aged mice calls for clinical investigation into potential beneficial effects of exercise on septic outcomes in the elderly.

Dataset Information

Aged mice are unable to mount an effective myeloid response to sepsis.

Publications

Aged mice are unable to mount an effective myeloid response to sepsis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets