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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 -
European Journal of Pediatrics Apr 2024Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However,... (Meta-Analysis)
Meta-Analysis
Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67-7.52) and defervescence rate (OR = 5.01, 95% CI 2.99-8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61-1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65-2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02-5.01) and a larger reduction of right coronary artery Z score (MD = -0.24, 95% CI -0.27 to -0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups. Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD. What is Known: • Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders. • The efficacy of infliximab in treating children with Kawasaki disease is controversial. What is New: • Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.
Topics: Child; Humans; Infant; Infliximab; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Tumor Necrosis Factor-alpha; Antibodies, Monoclonal
PubMed: 38240765
DOI: 10.1007/s00431-024-05437-2 -
Inflammopharmacology Feb 2024Although a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its beneficial health effects. Hence, the purpose of this study was to examine the effect of acarbose on inflammatory cytokines and adipokines in adults.
METHODS
PubMed, Web of Science, and Scopus were systematically searched until April 2023 using relevant keywords. The mean difference (MD) of any effect was calculated using a random-effects model. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated via the random-effects model.
RESULTS
The current meta-analysis of data comprised a total of 19 RCTs. Meta-analysis showed that acarbose significantly decreased tumor necrosis factor-alpha (TNF-α) (weighted mean difference [WMD]) = - 4.16 pg/ml, 95% confidence interval (CI) - 6.58, - 1.74; P = 0.001) while increasing adiponectin (WMD = 0.79 ng/ml, 95% CI 0.02, 1.55; P = 0.044). However, the effects of acarbose on TNF-α concentrations were observed in studies with intervention doses ≥ 300 mg/d (WMD = - 4.09; 95% CI - 7.00, - 1.18; P = 0.006), and the adiponectin concentrations were significantly higher (WMD = 1.03 ng/ml, 95%CI 0.19, 1.87; P = 0.016) in studies in which the duration of intervention was less than 24 weeks. No significant effect was seen for C-reactive protein (CRP; P = 0.134), interleukin-6 (IL-6; P = 0.204), and leptin (P = 0.576).
CONCLUSION
Acarbose had beneficial effects on reducing inflammation and increasing adiponectin. In this way, it may prevent the development of chronic diseases related to inflammation. However, more studies are needed.
Topics: Adult; Humans; Adipokines; Cytokines; Acarbose; Adiponectin; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Interleukin-6; Inflammation
PubMed: 38170330
DOI: 10.1007/s10787-023-01401-y -
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 -
Clinical Rheumatology Mar 2024Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks.
METHODS
A systematic review, performed on PubMed (including Medline), Cochrane (CENTRAL) and DOAJ databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group.
RESULTS
Eighteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNFα inhibitors (TNFi), three for IL-17 inhibitors, and four for JAK inhibitors. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI - 4.25; - 2, 34]), by IL-17 inhibitors (WMD: - 4.66 [95% CI - 6.22; - 3.09]), and by JAK inhibitors (JAKi) (WMD: - 3.06 [95% CI - 3.24; - 2.89]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors reduced more SIJ SPARCC, but not significantly (WMD: - 2.26 [95% CI - 4.94; 0.42]), than placebo groups who began a TNFi treatment with delay.
CONCLUSION
Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi, and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Key Points • Anti-TNF Ab, anti-IL17 Ab, and JAK inhibitor treatments reduce the sacroiliac joint SPARCC scores. • There is no difference between the different treatments in the reduction of the sacroiliac joint SPARCC score after 3 months in axial spondyloarthritis.
Topics: Humans; Spondylarthritis; Interleukin-17; Tumor Necrosis Factor-alpha; Janus Kinase Inhibitors; Tumor Necrosis Factor Inhibitors; Sacroiliac Joint; Antirheumatic Agents; Axial Spondyloarthritis; Magnetic Resonance Imaging
PubMed: 38158505
DOI: 10.1007/s10067-023-06849-5 -
Journal of Psychiatric Research Jan 2024Early adverse experience is related to psychiatric illness that occurs decades later. The mechanisms underlying this phenomenon have not been fully identified. There is... (Review)
Review
UNLABELLED
Early adverse experience is related to psychiatric illness that occurs decades later. The mechanisms underlying this phenomenon have not been fully identified. There is a translational and clinical literature linking early adversity with Major Depressive Disorder (MDD) and inflammation. We reviewed articles that examine whether inflammation mediates this relationship.
METHODS
Literature review of PUB MED, CINAHL and APA Psycinfo articles that explicitly examine inflammation as a mediator between early adversity and depression using ((((((((((adversity) OR (trauma)) OR (maltreatment)) OR (child abuse)) AND (inflammation)) OR (inflammatory cytokines)) OR (crp)) OR (il-6)) OR (tnf)) AND (mediates)) AND (depression))))))))) as key words.
RESULTS
2842 articles were initially identified. 1338 non-human studies were excluded and 512 more were filtered out as reviews. The remaining 992 titles and, when necessary, abstracts and manuscripts were reviewed and 956 were removed as being of other non-related phenomena. Four additional studies were added by hand searching the references of remaining studies. Out of these 40, 15 explicitly examined inflammation as a mediator of the relationship between early adversity and later depression. Approximately half (8/15) showed evidence that inflammation mediated the relationship between early adversity and depression. Sensitivity analyses showed that studies taking place in clinical populations, in youth and those that used the Adverse Childhood Events Scale to measure adversity, and IL-6 and TNF-α (as opposed to CRP) to measure inflammation were most likely to show mediation.
CONCLUSIONS
There is evidence to support the model of inflammation mediating the relationship between early adversity and depression. Certain measures in clinical populations appear more likely to support this model. Further study with more standardized, robust methods will help to answer this question more definitively and may elucidate a subtype of depression related to early adversity by alterations in immune function.
Topics: Humans; Child; Adolescent; Depressive Disorder, Major; Interleukin-6; Inflammation; Cytokines; Tumor Necrosis Factor-alpha
PubMed: 38154266
DOI: 10.1016/j.jpsychires.2023.11.025 -
The Australasian Journal of Dermatology Mar 2024Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of...
BACKGROUND/OBJECTIVES
Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics.
METHODS
Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records. A snowballing method was employed to search the references of the retrieved records for the identification of potentially relevant articles.
RESULTS
One hundred and four eligible studies consisting of a total of 166 patients with an inherited disorder of keratinisation were included. Patients had a median age of 19 years (range: 0.5 to 70 years). The most common disorders were Netherton syndrome (n = 63; 38%), autosomal recessive congenital ichthyoses (n = 27; 16%), CARD14-associated papulosquamous eruptions (n = 17; 10%) and familial pityriasis rubra pilaris (PRP) (n = 15; 9%).Of the 207 times biologics were employed, the three most frequently employed biologics were secukinumab (n = 47; 23%), dupilumab (n = 44; 21%) and ustekinumab (n = 37; 18%). Complete remission was observed in 10 (5%) instances, partial remission in 129 (62%), no or limited response to biologic therapy in 68 (32%) cases, and results are still pending in one case. A total of 33 adverse events were reported.
CONCLUSIONS
Whilst biologics may be considered in cases of inherited keratinisation disorders recalcitrant to standard therapy, definitive conclusions are prohibited by the low-level of evidence and substantial heterogeneity in methodology across the included studies. Establishment of consensus definitions, and randomised clinical trials may help ascertain the efficacy and safety of biologic therapy in this context and establish the best agent and dosing protocol for each disorder.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Biological Products; Ustekinumab; Tumor Necrosis Factor-alpha; Pityriasis Rubra Pilaris; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins
PubMed: 38126177
DOI: 10.1111/ajd.14197 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2024Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.
METHODS
We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.
RESULTS
Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo.
CONCLUSION
Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.
Topics: Humans; Biological Products; Incidence; Antirheumatic Agents; Network Meta-Analysis; Axial Spondyloarthritis; Antibodies, Monoclonal; Interleukin-17; Etanercept; Janus Kinase Inhibitors; Uveitis, Anterior; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Uveitis
PubMed: 38116697
DOI: 10.1002/art.42788