Immunosenescence in persons with spinal cord injury in relation to urinary tract infections -a cross-sectional study-

Pavlicek, David; Krebs, Jörg; Capossela, Simona; Bertolo, Alessandro; Engelhardt, Britta; Pannek, Jürgen; Stoyanov, Jivko

doi:10.1186/s12979-017-0103-6

Cited by 26 publications

(25 citation statements)

References 38 publications

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“… 20 , 25 It is possible that pain still persists, while NSAIDs and other anti-inflammatory molecules lower the levels of pro-inflammatory cytokines. We show, in another study, 38 that people with spinal cord injury (SCI) had, despite higher infection rates and elevated serum C-reactive protein concentrations, lower plasma levels of TNF-α and other cytokines when compared with age matched able bodied healthy controls. Similar to the chronic back pain patients, persons with SCI consume above-average NSAIDs, antidepressants, and muscle-relaxants.…”

Section: Discussionmentioning

confidence: 87%

Unexpectedly decreased plasma cytokines in patients with chronic back pain

Capossela¹,

Pavlicek²,

Bertolo³

et al. 2018

JPR

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IntroductionChronic back pain is one of the most important socioeconomic problems that affects the global population. Elevated levels of inflammatory mediators, such as cytokines, have been correlated with pain, but their role in chronic back pain remains unclear. The effectiveness of anti-inflammatory drugs seems to be limited for chronic back pain. The authors wanted to investigate the levels of inflammatory mediators in long-term medically treated patients with persistent chronic back pain.MethodsCytokine plasma levels of patients with chronic back pain (n=23), compared to pain-free healthy controls (n=30), were investigated by immunoassay. Patients with chronic back pain were exposed to long-term conservative medical therapy with physiotherapy and anti-inflammatories, also combined with antidepressants and/or muscle-relaxants.ResultsThe patients with chronic back pain expressed lower levels of the chemokines MCP1, CCL5, and CXCL6 compared to pain-free healthy controls. Significantly lower concentrations of the anti-inflammatory cytokines, interleukin (IL)-4 and granulocyte-colony stimulating factor were also found. Interestingly, levels of proinflammatory cytokines (IL-2, IL-6, IL-1β, tumor necrosis factor alpha), IL-10, granulocyte-macrophage colony-stimulating factor, and stromal cell-derived factor 1 alpha showed no significant differences between both groups.ConclusionThis decrease of inflammatory mediators in medically treated patients with chronic back pain is of unclear origin and might be either a long-term side effect of medical therapy or related to chronic pain. Further longitudinal research is necessary to elucidate the underlying cause of these findings.

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Section: Discussionmentioning

confidence: 87%

Unexpectedly decreased plasma cytokines in patients with chronic back pain

Capossela¹,

Pavlicek²,

Bertolo³

et al. 2018

JPR

Self Cite

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“…Additionally, cathepsins are known to regulate senescence (Byun et al 2009) and pathogenesis of age-related disease (Nixon et al 2000) and are also secreted by senescent cells (Basisty et al 2020). Moreover, the upregulation of ANXA1 and CTSD has been reported as candidate biomarkers of spinal cord injury (Moghieb et al 2016) which involves the appearance of senescent cells (Pavlicek et al 2017;Swenson et al 2019;Takano et al 2017). Finally, both the β-galactoside-binding proteins galectin-3 (LGALS3) and galectin-7 (LGALS7) were significantly upregulated in senescent HMECs.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Proteomic Signature of Senescence in Primary Human Mammary Epithelial Cells

Delfarah

Zheng

et al. 2020

Preprint

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Cellular senescence is the natural program by which cells enter a permanent cell cycle arrest in response to stresses including replicative exhaustion, oncogenic signaling, or DNA damage. Although senescence exerts beneficial effects by acting as a barrier against tumorigenesis, senescent cells can also drive chronic inflammation and age-related diseases through secretion of cytokines and other inflammatory proteins. Therefore, the identification of senolytic compounds that specifically eliminate senescent cells has become an area of great therapeutic promise. Here, we used mass spectrometry-based proteomics to identify senescence biomarkers in primary human mammary epithelial cells (HMECs), a model system for aging. By integrating proteomic data from replicative senescence, immortalization by telomerase reactivation, and drug-induced senescence, we identified a robust HMEC proteomic signature of senescence consisting of 57 upregulated and 29 downregulated proteins. This senescence signature identified both well-known senescence biomarkers, including downregulation of the nuclear lamina protein lamin-B1 (LMNB1), as well as novel biomarkers such as upregulation of the β-galactoside-binding protein galectin-7 (LGALS7). Then, we integrated our proteomic signature of senescence with large-scale drug screening databases to predict that EGFR inhibitors, MEK inhibitors, and dasatinib are novel senolytics in HMEC. Taken together, our results support that the combination of quantitative proteomics and public drug screening databases is a powerful approach to identify senescence biomarkers and novel senolytic compounds.

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“…Transurethral catheters showed the highest odds of UTI [13]. In addition, it has been demonstrated that SCI induces an immune deficiency syndrome that is sufficient to propagate clinical relevant infections in these patients [14, 15]. As only a minority of the underlying causes can be treated effectively, the risk for recurrent UTI in this group of patients is higher than that in the general population, leading to recurrent antibiotic treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, prognostic factors that enable us to assess the risk in each individual patient are lacking. Preliminary data give a hint that the state of the immune system correlates with UTI development [15]. Future studies may therefore identify predictive tests that enable physicians to stratify antibiotic treatment based on individual risk factors.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Complicated Urinary Tract Infections in Individuals with Chronic Neurogenic Lower Urinary Tract Dysfunction: Are Antibiotics Mandatory?

2018

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Introduction: Urinary tract infections (UTI) in patients with neurogenic lower urinary tract dysfunction (NLUTD) are defined as complicated UTI requiring antibiotic treatment. As the emergence of multiresistant strains is a serious problem, we assessed the feasibility of nonantibiotic treatment of UTI in patients with NLUTD. Materials and Methods: In a prospective study evaluating the usefulness of UTI prophylaxis, participants could opt for either antibiotic or nonantibiotic treatment of breakthrough UTI. If either symptoms persisted for 48 h or a febrile UTI occurred, antibiotic treatment based on microbiological testing was mandatory. Treatment efficacy, complications, and emergency hospital visits were assessed. Results: Within the observation period (1 year), the 25 participants developed 206 UTI. Seven febrile UTI required immediate antibiotic treatment. Of the remaining 199 UTI, patients chose antibiotic treatment in 104 events, whereas in 95 events, patients chose either nonantibiotic interventions (n = 80) or no treatment at all (n = 15). Success rates were 78.8% for antibiotic treatment, 67.5% with nonantibiotic treatments, and 26% without therapy. Of the 7 patients with initially febrile UTI, 2 required hospitalization due to septicemia. Conclusions: Nonantibiotic treatment seems to be a feasible alternative to antibiotic therapy in patients with complicated UTI as well, provided there is no fever.

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Immunosenescence in persons with spinal cord injury in relation to urinary tract infections -a cross-sectional study-

Cited by 26 publications

References 38 publications

Unexpectedly decreased plasma cytokines in patients with chronic back pain

Unexpectedly decreased plasma cytokines in patients with chronic back pain

Identification of a Proteomic Signature of Senescence in Primary Human Mammary Epithelial Cells

Treatment of Complicated Urinary Tract Infections in Individuals with Chronic Neurogenic Lower Urinary Tract Dysfunction: Are Antibiotics Mandatory?

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