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Pain Physician Feb 2024Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between...
BACKGROUND
Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between immune, neuro, and glial cells contributes to chronic pain.
OBJECTIVES
This study systematically reviewed cytokine levels and their relation to chronic cancer-related pain and, additionally, investigated differences in cytokine levels between cancer survivors with and without chronic pain.
STUDY DESIGN
Systematic review.
METHODS
This systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The study conducted a systematic literature search in the databases PubMed, Web of Science, and Embase for articles examining cytokine levels and pain experience at a time point of a minimum of 3 months post-cancer diagnosis. Pain experience was categorized into a total pain score, pain intensity, and pain interference. The risk of bias was assessed using the Newcastle Ottawa Scale.
RESULTS
Eight articles were included, investigating 6 cancer types and 30 cytokines. Moderate evidence was found for pro-inflammatory cytokine IL-6 to be correlated with pain intensity, of which higher levels are observed in cancer survivors experiencing chronic pain compared to pain-free survivors. Moderate evidence was found for TNF-alpha to be not correlated with any pain experience, which is similar for anti-inflammatory cytokines IL-8 and IL-10 with pain intensity. For the remaining 26 cytokines and pain outcomes, only limited evidence was found for an association or alteration.
LIMITATIONS
The number of included studies was small. Overall, studies showed a moderate risk of bias, except one indicated a high risk of bias.
CONCLUSION
More standardized post-cancer treatment studies are warranted to confirm these results and explore associations and alterations of other cytokines. Nonetheless, moderate evidence suggests that elevated levels of IL-6, in contrast with TNF-alpha levels, are correlated with pain intensity in cancer survivors experiencing chronic pain compared to pain-free survivors.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Chronic Pain; Interleukin-6; Cancer Survivors; Cancer Pain; Neoplasms
PubMed: 38324786
DOI: No ID Found -
Reviews in Medical Virology Jan 2024The activities of HIV-1 in the central nervous system (CNS) are responsible for a dysregulated neuroinflammatory response and the subsequent development of... (Review)
Review
The relationship between HIV-1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post-mortem brain tissue.
The activities of HIV-1 in the central nervous system (CNS) are responsible for a dysregulated neuroinflammatory response and the subsequent development of HIV-associated neurocognitive disorders (HAND). The use of post-mortem human brain tissue is pivotal for studying the neuroimmune mechanisms of CNS HIV infection. To date, numerous studies have investigated HIV-1-induced neuroinflammation in post-mortem brain tissue. However, from the commonly investigated studies in this line of research, it is not clear which neuroinflammatory markers are consistently associated with HIV neurocognitive impairment (NCI) and neuropathology (i.e., HIV-encephalitis, HIVE). Therefore, we conducted a systematic review of the association between neuroinflammation and NCI/HIVE from studies investigating post-mortem brain tissue. Our aim was to synthesise the published data to date to provide commentary on the most noteworthy markers that are associated with NCI/HIVE. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Sixty-one studies were included that investigated the levels of inflammatory markers based on their gene and protein expression in association with NCI/HIVE. The findings revealed that the (1) transcript expressions of IL-1β and TNF-α were consistently associated with NCI/HIVE, whereas CCL2 and IL-6 were commonly not associated with NCI/HIVE, (2) protein expressions of CD14, CD16, CD68, Iba-1, IL-1β and TNF-α were consistently associated with NCI/HIVE, while CD45, GFAP, HLA-DR, IL-1 and IL-6 were commonly not associated with NCI/HIVE, and (3) gene and protein expressions of CNS IL-1β and TNF-α were consistently associated with NCI/HIVE, while IL-6 was consistently not associated with NCI/HIVE. These markers highlight the commonly investigated markers in this line of research and elucidates the neuroinflammatory mechanisms in the HIV-1 brain that are involved in the pathophysiology of NCI/HIVE. These markers and related pathways should be investigated for the development of improved diagnostics, prognostics, and therapeutics of HAND.
Topics: Humans; HIV Infections; HIV-1; Neuroinflammatory Diseases; Tumor Necrosis Factor-alpha; Interleukin-6; Brain; Encephalitis; HIV Seropositivity
PubMed: 38282400
DOI: 10.1002/rmv.2519 -
Frontiers in Immunology 2023This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by...
INTRODUCTION
This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.
METHODS
Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients.
RESULTS
From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile.
CONCLUSION
Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.
Topics: Humans; Acne Vulgaris; Adaptor Proteins, Signal Transducing; Antibodies, Monoclonal, Humanized; Arthritis, Infectious; Cytoskeletal Proteins; Interleukin 1 Receptor Antagonist Protein; Interleukin-1
PubMed: 38259483
DOI: 10.3389/fimmu.2023.1339337 -
Scientific Reports Jan 2024This systematic review and meta-analysis aimed to determine the magnitude of the effect of combined exercise training on glucose metabolism markers, adipokines, and... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to determine the magnitude of the effect of combined exercise training on glucose metabolism markers, adipokines, and inflammatory cytokines in non-diabetic sedentary adults. PubMed, Web of Science, Scopus, Cochrane Library electronic databases and reference lists of included studies were explored for randomized controlled trials (RCTs) that included physically inactive adults and provided combined training interventions (aerobic plus resistance exercise). Effects on fasting glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HbA1c, adiponectin, leptin, IL-6, TNF-α, and C-reactive protein (CRP) in exercise vs control groups were analyzed using random effects meta-analysis. The Cochrane Risk of Bias Tool for Randomized Trials 2.0 (RoB 2) was used to assess the risk of bias. A total of 24 RCTs were included in the quantitative analysis. Combined exercise training significantly decrease fasting glucose (standardized mean difference, SMD: - 0.474, 95% CI [- 0.829, - 0.120], p = 0.009, 35 study arms), fasting insulin (SMD: - 1.024, 95% CI [- 1.502, - 0.545], p < 0.001, 27 study arms), HOMA-IR (SMD: - 0.946, 95% CI [- 1.450, - 0.442], p < 0.001, 23 study arms), TNF-α (SMD: - 0.972, 95% CI [- 1.361, - 0.582], p < 0.001, 10 study arms), and CRP (SMD: - 0.507, 95% CI [- 0.818, - 0.196], p = 0.001, 14 study arms). No significant effects were observed for HbA1c, adiponectin, leptin, and IL-6 levels. Random effects meta-regression models by age, sex, and intervention length were not able to explain any of the variation in the effect size of HOMA-IR. Findings from this systematic review and meta-analysis suggest that combined exercise training improves some glucose metabolism markers and inflammatory parameters in sedentary adults without diabetes.
Topics: Adult; Humans; Adiponectin; Glycated Hemoglobin; Interleukin-6; Leptin; Tumor Necrosis Factor-alpha; Insulin; C-Reactive Protein; Exercise; Glucose
PubMed: 38253590
DOI: 10.1038/s41598-024-51832-y -
PloS One 2024This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data from eligible studies.
MATERIALS AND METHODS
Through a comprehensive searching of pubmed, embase, web of science, cochrane from establishment of the database to October 31, 2022, studies were selected that investigated the association of circulating cell free mitochondria DNA with inflammatory factors in non-infectious diseases. Studies that met the inclusion criteria and were published in English or Chinese were included. Data of each correlation coefficients were extracted from the paper and 95% confidence intervals were calculated. Sensitivity and heterogeneity tests were carried out for each data.
RESULTS
A total of 660 articles were retrieved and 22 were included in this meta-analysis, including 2600 patients. A fixed effects model was employed to examine ISS and IL-8, others were analyzed using random effects models. The correlation coefficient between mtDNA and ISS score was 0.37 (95%CI = [0.232;0.494]), p<0.0001, heterogeneity I2 = 46%, p = 0.11). The correlation coefficients between mtDNA and inflammatory factors are as follows: TNFα, 0.405 [(95%CI = [0.253;0.538], p<0.0001, heterogeneity I2 = 77%, p = 0.0001]. IL-6, 0.469 [(95%CI = [0.296;0.612]), p = 0.0001, heterogeneity I2 = 93%, p<0.0001]. CRP, 0.333[(95%CI = [0.149;0.494]), p = 0.005, heterogeneity I2 = 85%, p<0.0001]. IL-8, 0.343[(95%CI = [0.233;0.524]), p = 0.001, heterogeneity I2 = 50%, p = 0.09]. PCT, 0.333 [(95%CI = [0.06;0.64]), p = 0.09,heterogeneity I2 = 64%,p = 0.06]. There were no significant publication bias for TNFα, IL-6 and CRP.
CONSLUSION
Circulating cell free mtDNA was moderate positively correlated with the expression of inflammatory factors and the degree of trauma.
Topics: Humans; Noncommunicable Diseases; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-8; Inflammation; DNA, Mitochondrial; Mitochondria
PubMed: 38241222
DOI: 10.1371/journal.pone.0289338 -
Pharmacological Research Feb 2024Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature review and meta-analysis to study the associations between key cytokines and incident hypertension.
METHODS
We performed a systematic search of Pubmed/Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), for peer-reviewed studies published up to August 2022. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medications. Random effects meta-analyses were used to calculate pooled hazard ratios (HRs)/risk ratios (RRs) and 95% confidence intervals by cytokine levels (highest vs. lowest quartile).
RESULTS
Only IL-6 and IL-1β levels have evidence allowing for quantitative evaluation concerning the onset of hypertension. Six studies (10406 participants, 2932 incident cases) examined the association of IL-6 with incident hypertension. The highest versus lowest quartile of circulating IL-6 was associated with a significant HR/RR of hypertension (1.61, 95% CI: 1.00 to 2.60; I =87%). After adjusting for potential confounders, including body mass index (BMI), HR/RR was no longer significant (HR/RR: 1.24; 95% CI, 0.96 to 1.61; I = 56%). About IL-1β, neither the crude (HR/RR: 1.03; 95% CI, 0.60 to 1.76; n = 2) nor multivariate analysis (HR/RR: 0.97, 95% CI, 0.60 to 1.56; n = 2) suggested a significant association with the risk of developing hypertension.
CONCLUSIONS
A limited number of studies suggest that higher IL-6, but not IL-1β, might be associated with the development of hypertension.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Cytokines; Hypertension; Interleukin-1beta; Interleukin-6
PubMed: 38159784
DOI: 10.1016/j.phrs.2023.107050 -
Medicine Dec 2023Immunobiological drugs such as TNF-α inhibitors are valuable in rescue therapy for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immunobiological drugs such as TNF-α inhibitors are valuable in rescue therapy for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (IBD), but they increase the risk of infectious complications. Histoplasmosis is a significant concern in patients living in endemic regions, however, few studies have assessed the incidence of Histoplasma infection during therapy, and classic estimates may underestimate the risk. This study aimed to produce an updated risk estimate of histoplasmosis in patients on TNF-α blocking therapy.
METHODS
This is a systematic review and meta-analysis of studies that contain parameters for calculating the risk of histoplasmosis in people who use TNF-α inhibitors, to produce a risk estimate.
RESULTS
We identified 11 studies with the necessary parameters for inclusion in the meta-analysis, most of which were from North America. The incidence rate of histoplasmosis found was 33.52 cases per 100,000 patients treated with TNF-ɑ inhibitors (95% CI 12.28-91.46). Considering only studies evaluating monoclonal antibodies, the calculated incidence was 54.88/100,000 patients treated (95%CI 23.45-128.34). In subgroup analysis, the incidence was much higher in patients with IBD compared to rheumatic diseases. There was significant heterogeneity among the studies.
CONCLUSION
The risk of histoplasmosis during TNF-α inhibitory therapy may be considerably higher than that found in classical estimates, especially in patients with IBD. There is a lack of studies evaluating histoplasmosis in large endemic areas, such as Central and South America.
Topics: Humans; Tumor Necrosis Factor-alpha; Histoplasmosis; Incidence; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases
PubMed: 38065857
DOI: 10.1097/MD.0000000000036450 -
Critical Care (London, England) Nov 2023Bacteria are the main pathogens that cause sepsis. The pathogenic mechanisms of sepsis caused by gram-negative and gram-positive bacteria are completely different, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacteria are the main pathogens that cause sepsis. The pathogenic mechanisms of sepsis caused by gram-negative and gram-positive bacteria are completely different, and their prognostic differences in sepsis remain unclear.
METHODS
The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for Chinese and English studies (January 2003 to September 2023). Observational studies involving gram-negative (G (-))/gram-positive (G (+)) bacterial infection and the prognosis of sepsis were included. The stability of the results was evaluated by sensitivity analysis. Funnel plots and Egger tests were used to check whether there was publication bias. A meta-regression analysis was conducted on the results with high heterogeneity to identify the source of heterogeneity. A total of 6949 articles were retrieved from the database, and 45 studies involving 5586 subjects were included after screening according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-seven high-quality studies and 18 moderate-quality studies were identified according to the Newcastle‒Ottawa Scale score. There was no significant difference in the survival rate of sepsis caused by G (-) bacteria and G (+) bacteria (OR 0.95, 95% CI 0.70-1.28). Subgroup analysis according to survival follow-up time showed no significant difference. The serum concentrations of C-reactive protein (CRP) (SMD = 0.39, 95% CI 0.02-0.76), procalcitonin (SMD = 1.95, 95% CI 1.32-2.59) and tumor necrosis factor-alpha (TNF-α) (MD = 0.31, 95% CI 0.25-0.38) in the G (-) bacterial infection group were significantly higher than those in the G (+) bacterial infection group, but there was no significant difference in IL-6 (SMD = 1.33, 95% CI - 0.18-2.84) and WBC count (MD = - 0.15, 95% CI - 0.96-00.66). There were no significant differences between G (-) and G (+) bacteria in D dimer level, activated partial thromboplastin time, thrombin time, international normalized ratio, platelet count, length of stay or length of ICU stay. Sensitivity analysis of the above results indicated that the results were stable.
CONCLUSION
The incidence of severe sepsis and the concentrations of inflammatory factors (CRP, PCT, TNF-α) in sepsis caused by G (-) bacteria were higher than those caused by G (+) bacteria. The two groups had no significant difference in survival rate, coagulation function, or hospital stay. The study was registered with PROSPERO (registration number: CRD42023465051).
Topics: Humans; Prognosis; Tumor Necrosis Factor-alpha; Sepsis; Bacterial Infections; Gram-Negative Bacteria; C-Reactive Protein; Bacteria; Gram-Positive Bacteria
PubMed: 38037118
DOI: 10.1186/s13054-023-04750-w -
Autoimmunity Reviews Mar 2024To report cases of new onset sarcoidosis upon biologic (bDMARDs) treatment administration in patients with seronegative inflammatory arthritis in a real-life cohort,... (Review)
Review
OBJECTIVE
To report cases of new onset sarcoidosis upon biologic (bDMARDs) treatment administration in patients with seronegative inflammatory arthritis in a real-life cohort, alongside a systematic literature review (SLR) on this topic.
METHODS
We performed a retrospective analysis on clinical records of patients with seronegative arthritis followed up in a monocentric cohort who underwent bDMARDs treatment due to the underlying rheumatic disease and described any newly diagnosed sarcoidosis in this cohort. Only ascertained cases with available radiological and/or histological documentation were considered. A SLR on new-onset sarcoidosis in seronegative arthritis receiving bDMARDs was performed across MEDLINE (through PubMed), Scopus and Ovid (Cochrane, Embase) electronic databases using appropriate strings.
RESULTS
In our cohort, 4 new-onset cases of sarcoidosis were reported among patients with seronegative inflammatory arthritis receiving biologics. Three out of 4 patients were receiving anti-tumor necrosis factor alpha (TNFα) while 1 patient was on secukinumab (anti-IL17A) prior to sarcoidosis onset. The SLR disclosed 46 new-onset sarcoidosis cases upon biological treatment for seronegative arthritis, of whom 43 occurred during treatment with anti-TNFα, while 3 during anti-IL-17A therapy. In our cohort as well as in the majority of cases reported in the SLR, sarcoidosis presented with lymph nodal and lung involvement and displayed a benign course with spontaneous resolution in about 1 fourth of the cases.
CONCLUSION
The use of biologics may relate to the onset of sarcoidosis; hence, clinicians must remain aware of the potential occurrence or reactivation of sarcoidosis when starting biologic treatment in patients with inflammatory arthritis, performing adequate patient assessment and surveillance. Since TNFα inhibitors may represent a therapeutic option for sarcoidosis, further evaluation on larger cohorts is needed to investigate any causal link with the development of sarcoidosis.
Topics: Adult; Female; Humans; Middle Aged; Antirheumatic Agents; Arthritis; Biological Products; Retrospective Studies; Sarcoidosis; Tumor Necrosis Factor-alpha
PubMed: 38008299
DOI: 10.1016/j.autrev.2023.103481 -
Chinese Medical Journal Feb 2024
Meta-Analysis
Topics: Humans; Arthritis, Psoriatic; Interleukin-17; Interleukin Inhibitors; Antirheumatic Agents; Tumor Necrosis Factor-alpha; Interleukin-23
PubMed: 37989584
DOI: 10.1097/CM9.0000000000002860