Reduction of Immunocompetent T Cells Followed by Prolonged Lymphopenia in Severe Sepsis in the Elderly*

Inoue, Shigeaki; Suzuki-Utsunomiya, Kyoko; Okada, Yoshinori; Taira, Takayuki; Iida, Yumi; Miura, Naoya; Tsuji, Tomohiro; Yamagiwa, Takeshi; Morita, Seiji; Chiba, Tomoki; Sato, Takehito; Inokuchi, Sadaki

doi:10.1097/ccm.0b013e318274645f

Cited by 141 publications

(130 citation statements)

References 40 publications

(39 reference statements)

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“…Pneumococci were cultured from brain tissue associated with neutrophilic inflammation at the meninges. Pneumococcal bacteremia in mice was also associated with leukopenia, an observation that is consistent with the lymphopenia and splenic lymphocyte apoptosis described in septic patients and mouse models of sepsis (38)(39)(40). Moreover, all endpoint mice had detectable serum IL-6, which is thought to predict organ dysfunction and mortality in sepsis (41,42).…”

Section: Discussionsupporting

confidence: 54%

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

et al. 2016

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Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1␣ (IL-1␣) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.

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Section: Discussionsupporting

confidence: 54%

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

et al. 2016

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“…Recent studies on sepsis have focused on the role of T cells. Some clinical research studies declared that the percentage of immunocompetent CD4 + CD28 + T cells decreased, whereas the proportion of immunosuppressive PD-1 + T cells as well as Tregs increased, in septic patients, especially nonsurvivors, presumably reflecting the initial signs of immunosuppression [18,19]. Monocyte dysfunction (such as the apoptosis-induced loss of B cells and dendritic cells) was identified in patients with sepsis [20]; and the dysfunction of peripheral blood lymphocytes in sepsis was associated with a significant reduction of lymphocytes, CD4 + T cells, and CD8 + T cells as well as natural killer cells.…”

Section: Discussionmentioning

confidence: 98%

Fish oil–supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis

Li¹,

Zhang²,

Yang³

et al. 2015

Nutrition Research

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“…In septic shock, severe lymphopenia involves different lymphocyte subsets, and is associated with restricted diversity of the T-cell repertoire (5,6). Furthermore, elderly patients with severe lymphopenia during severe sepsis tend to have increased mortality (7).…”

Section: Introductionmentioning

confidence: 99%

Severe Lymphopenia Is Associated with Elevated Plasma Interleukin-15 Levels and Increased Mortality During Severe Sepsis

Chung¹,

Chang

et al. 2015

Shock

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Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 10(3)/μL. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor α, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482-8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.

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Reduction of Immunocompetent T Cells Followed by Prolonged Lymphopenia in Severe Sepsis in the Elderly*

Abstract: Reduction of immunocompetent T cells followed by prolonged lymphopenia may be associated with poor prognosis in elderly septic patients.

Cited by 141 publications

References 40 publications

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

Fish oil–supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis

Severe Lymphopenia Is Associated with Elevated Plasma Interleukin-15 Levels and Increased Mortality During Severe Sepsis

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