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      Cytokines and chemokines profile in encephalitis patients: A meta-analysis

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          Abstract

          Background

          Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum.

          Methods

          We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298.

          Results

          A total of 23 met our eligibility criteria to be included in the meta-analysis. A total of 12 cytokines were included in the meta-analysis of CSF concentration. Moreover, 5 cytokines were also included in the serum/plasma concentration meta-analysis. According to the analyses, patients with encephalitis had higher CSF amounts of IL-6, IL-8, IL-10, CXCL10, and TNF-α than healthy controls. The alteration in the concentration of IL-2, IL-4, IL-17, CCL2, CXCL9, CXCL13, and IFN-γ was not significant. In addition, the serum/plasma levels of the TNF-α were increased in encephalitis patients, but serum/plasma concentration of the IL-6, IL-10, CXCL10, and CXCL13 remained unchanged.

          Conclusions

          This meta-analysis provides evidence for higher CSF concentrations of IL-6, IL-8, IL-10, CXCL10, and TNF-α in encephalitis patients compared to controls. The diagnostic and prognostic value of these cytokines and chemokines should be investigated in future studies.

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          Most cited references219

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          Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range

          Background In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials. Methods In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.’s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials. Results We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications. Conclusions In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations. Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-14-135) contains supplementary material, which is available to authorized users.
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            Cochrane Handbook for Systematic Reviews of Interventions

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              Meta-analysis in clinical trials.

              This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 September 2022
                2022
                : 17
                : 9
                : e0273920
                Affiliations
                [1 ] School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                [2 ] Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
                [3 ] Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
                [4 ] Non–Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
                [5 ] Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
                [6 ] Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                National Institute of Allergy and Infectious Diseases, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-5305-4219
                https://orcid.org/0000-0003-2426-6340
                https://orcid.org/0000-0002-3836-1827
                Article
                PONE-D-22-04861
                10.1371/journal.pone.0273920
                9436077
                36048783
                9b4cf7eb-3af1-411e-88a9-7569566723de
                © 2022 Soltani Khaboushan et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 February 2022
                : 17 August 2022
                Page count
                Figures: 8, Tables: 3, Pages: 34
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Infectious Diseases of the Nervous System
                Encephalitis
                Medicine and Health Sciences
                Neurology
                Infectious Diseases of the Nervous System
                Encephalitis
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Cytokines
                Biology and Life Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Medicine and Health Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Biology and Life Sciences
                Developmental Biology
                Molecular Development
                Cytokines
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Metaanalysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Metaanalysis
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Cerebrospinal Fluid
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Cerebrospinal Fluid
                Biology and Life Sciences
                Physiology
                Body Fluids
                Cerebrospinal Fluid
                Biology and Life Sciences
                Anatomy
                Nervous System
                Cerebrospinal Fluid
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Cerebrospinal Fluid
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Science Policy
                Research Integrity
                Publication Ethics
                Biology and Life Sciences
                Cell Biology
                Cell Motility
                Chemotaxis
                Chemokines
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Inflammation
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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