TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin ...expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = − 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies.
•Expression of TLR4 in neutrophils was higher in HD than CKD patients.•Expression of TLR4 in monocytes was higher in CKD than HD patients.•CKD and HD patients have high levels of TNF-α, IL-6, IL-10, MCP-1 and cathelicidin.•TLR4 had a correlation between TNF-α, IL-6, IL-10 MCP-1 and cathelicidin.•The uremic environment induces inflammation by TLR4, cathelicidin and cytokine activation.
The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate ...immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have ...been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio aOR = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.
The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate ...immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in ...vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus. Preliminary experiments verified that the surface pH of the human nasopharynx could be transiently lowered to pH ∼4.0 by topical administration of citrate/phosphate (CP) buffers, which was well tolerated. In a pilot experimental colds study, intranasal administration of CP buffer, compared with normal saline, reduced viral shedding by 1 log unit (103 vs. 104 50%tissue culture infective dose/mL; P < .01), although respiratory symptoms were not significantly reduced. These findings demonstrate that low-pH buffers have antiviral activity in vivo and suggest that a larger clinical trial is warranted to determine whether this approach could reduce rates of viral transmission.
The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate ...immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
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