Immune Tolerance as the Physiologic Counterpart of Chronic Inflammation

Rogovskii, Vladimir

doi:10.3389/fimmu.2020.02061

Cited by 25 publications

(8 citation statements)

References 73 publications

(90 reference statements)

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“…We propose some mechanisms that may explain this finding. As mentioned before, patients residing at high altitude are chronically exposed to slightly elevated levels of inflammatory factors, which consequently leads to adaptation and immune tolerance [25]. When infected by the virus, these patients may develop a less severe disease as their body is already adapted to elevated levels of inflammatory factors.…”

Section: Discussionmentioning

confidence: 97%

Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude

Valle-Mendoza

Tarazona-Castro

Merino-Luna³

et al. 2022

BMC Infect Dis

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Background At the end of 2019, a novel coronavirus denominated SARS-CoV-2 rapidly spread through the world causing the pandemic coronavirus disease known as COVID-19. The difference in the inflammatory response against SARS-CoV-2 infection among people living at different altitudes is a variable not yet studied. Methods A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN-γ and TNF-α using ELISA assays. Results A total of 35 COVID-19 patients and 10 healthy subjects were recruited from each study site. The mean levels of IL-6 (p < 0.03) and TNF-α (p < 0.01) were significantly different among the study groups. In the case of IL-6, patients from Lima had a mean level of 16.2 pg/ml (healthy) and 48.3 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 67.3 pg/ml (healthy) and 97.9 pg/ml (COVID-19). Regarding TNF-α, patients from Lima had a mean level of 25.9 pg/ml (healthy) and 61.6 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 89.0 pg/ml (healthy) and 120.6 pg/ml (COVID-19). The levels of IL-2, IL-10 and IFN-γ were not significantly different in the study groups. Conclusion Patients with COVID-19 residing at high-altitude tend to have higher levels of inflammatory cytokines compared to patients living at sea level, particularly IL-6 and TNF-α. A better understanding of the inflammatory response in different populations can contribute to the implementation of therapeutic and preventive approaches. Further studies evaluating more patients, a greater variety of cytokines and their clinical impact are required.

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Section: Discussionmentioning

confidence: 97%

Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude

Valle-Mendoza

Tarazona-Castro

Merino-Luna³

et al. 2022

BMC Infect Dis

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“…Indeed, it has been demonstrated that a modest increase in cytokine levels may be linked to immune tolerance [ 35 ]. Cytokines such as IL-6, IL-1 and IFN-γ are involved in the development of immune tolerance and, considering that different tumors may present a different cytokine profile in the TME, tolerance mechanisms may also vary in cancer subtypes [ 36 ]. Peripheral ignorance, which is due to the lack of tissue inflammation, is responsible for the absence of T cell recruitment instead [ 37 ].…”

Section: Factors Influencing T-cell Persistence In Clinical Settingsmentioning

confidence: 99%

Improving CAR T-Cell Persistence

Pietrobon

Todd

Goswami

et al. 2021

IJMS

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Over the last decade remarkable progress has been made in enhancing the efficacy of CAR T therapies. However, the clinical benefits are still limited, especially in solid tumors. Even in hematological settings, patients that respond to CAR T therapies remain at risk of relapsing due to several factors including poor T-cell expansion and lack of long-term persistence after adoptive transfer. This issue is even more evident in solid tumors, as the tumor microenvironment negatively influences the survival, infiltration, and activity of T-cells. Limited persistence remains a significant hindrance to the development of effective CAR T therapies due to several determinants, which are encountered from the cell manufacturing step and onwards. CAR design and ex vivo manipulation, including culture conditions, may play a pivotal role. Moreover, previous chemotherapy and lymphodepleting treatments may play a relevant role. In this review, the main causes for decreased persistence of CAR T-cells in patients will be discussed, focusing on the molecular mechanisms underlying T-cell exhaustion. The approaches taken so far to overcome these limitations and to create exhaustion-resistant T-cells will be described. We will also examine the knowledge gained from several key clinical trials and highlight the molecular mechanisms determining T-cell stemness, as promoting stemness may represent an attractive approach to improve T-cell therapies.

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“…Valle-Mendoza and colleagues, found that COVID-19 patients and healthy individuals living at high altitude had higher concentrations of inflammatory cytokines (IL-6 and TNF-α) than patients/individuals living at sea level. 28 This constant exposure to inflammatory factors has been proposed to induce an adaptation and immune tolerance 32 which ultimately might cause patients with COVID-19 to develop less severe disease. 28 Noninvasive respiratory support strategies used in this study such as HFNC and NIMV were lower compared to other studies treated COVID-19 patients, [33][34][35][36] 7.9% and 15.1%, respectively.…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study

Jibaja

Roldan-Vasquez

Rello

et al. 2022

J Intensive Care Med

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Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

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Immune Tolerance as the Physiologic Counterpart of Chronic Inflammation

Cited by 25 publications

References 73 publications

Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude

Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude

Improving CAR T-Cell Persistence

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study

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