REGISTRO DOI: 10.5281/zenodo.11640722
Andreza Gomes Pascoal1; Paula de Souza Mendes1; Lainara Pessoa de Souza1; Luiz Eduardo Rodrigues Lima2; Bruno Mori 3
Resumo
Interleukin-10 (IL-10) plays an important role in immune function in inflammation and physical activity demonstrated shortly with the synthesis of IL-10. We searched four databases up to February 20, 2023. Two reviewers screened the studies, collected data, assessed travel risk, and classified the evidence for each outcome across studies independently and in duplicate. The pre-specified endpoints of interest were physical activity; serum IL-10 levels; and Body Mass Index (BMI). We only included data from peer-reviewed articles in our primary analyses. In our primary analysis, there was a positive trend between serum IL-10 levels and body mass index; this result should be interpreted with caution. We identified 4 high-quality evidence that serum IL-10 levels and high physical activity are in a considered direct relationship. Although the evidence available to date, from medium-quality observational studies and clinical trials, can be seen as showing a trend toward the effectiveness of physical activity in obese children and adolescents and serum IL-10 levels, this relationship has been shown to have an effect stimulating. Serum IL-10 levels about low body mass index are not based on solid evidence. We await results from ongoing studies to determine this efficacy.
Keywords: child, adolescent, physical activity, Interleukin-10.
INTRODUCTION
Obesity is a metabolic disease with high prevalence in adults and has been associated with cardiometabolic risk factors, factors that have already been identified in obese children and adolescents as the basis for the manifestation of the disease in adulthood (Romeo, 2011). Considering this relationship, proposing changes to this reality should be an action developed preferably in childhood, since habits acquired at this stage are highly likely to be maintained in adult life (Trudeau et al., 2004; Ishak et al., 2013).
The prevalence of obesity in children and adolescents has doubled in the last three decades and has been associated with lifestyle changes, such as the type and amount of food eaten and a sedentary lifestyle. Increased adiposity has often been accompanied by increased levels of pro-inflammatory markers, associated with the emergence of other diseases such as diabetes mellitus and cardiovascular diseases (Lopes, 2016).
Physical activity and adiposity are factors that influence the inflammation process. As puberty is a critical period of growth considering that the body mass index (BMI) and the increase in sedentary behavior are amplified (Remmel, 2017), recommendations from the World Health Organization (WHO) for school-age children recommend carrying out, at least 60 minutes of daily physical activity must be followed for the protective effects of exercise to occur against possible chronic non-communicable diseases in schoolchildren (Duran et al., 2015; WHO, 2020; Kupèa et al., 2021).
Physical exercise, for decades, has been known to have a long-term protective effect against chronic non-communicable diseases. More recently, this protective effect has been associated with modulation induced by physical exercise (Rosa, 2011), such as the upregulation of anti-inflammatory cytokines, for example, IL-10 (Merlin M. et al., 2021).
IL-10 plays a crucial role in modulating the inflammatory response and regulating the balance between inflammation and immune tolerance. Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine with an important role in limiting the host’s immune response to pathogens by modulating tissue homeostasis (El Sehmawy AA. et al., 2022)
IL-10 also regulates the growth and/or differentiation of B cells, granulocytes, neutrophils, dendritic cells, keratinocytes, and endothelial cells. Various parasites, bacteria, fungi, and viruses depress the host’s immune response either by inducing the production of IL-10 or by encoding their own homologous IL-10. Despite being a potent immunosuppressant. Circulating levels of IL-10 are increased in allergic asthma, systemic sclerosis, obesity, hypovitaminosis, and sepsis (Matilainen et al., 2010; Amer & Quayyum, 2012; Al-Daghri et al., 2014).
IL-10 is produced mainly by activated CD8+ cells. Activated Th0, Th1, Th2 cells, B lymphocytes, mast cells, and monocytes activated by LPS can also produce IL-10, being less important sources. In monocytes, the vitamin D receptor negatively regulates IL-10 expression by binding to the promoter region (Al-Daghri et al., 2014; Melo et al., 2020; Mori et al., 2022).
However, to our knowledge, no systematic review has analyzed the effect of different doses of exercise in children and adolescents with the comparator obesity and serum IL-10 levels. Therefore, this study aimed to examine the effectiveness of physical activity in obese children and adolescents and serum interleukin-10 levels through a systematic review.
METHODS
The research was designed using the Cochrane collaboration recommendations for systematic reviews and reported according to the preferred reporting items for systematic reviews and meta-analysis(Moher D et al., 2009).
The initial selection was based on the titles and the abstract of manuscripts. The elegible articles were analyzed and the reference lists of them were evaluated. These steps were performed independently and conducted by two pairs of reviewers AGP/PSM), and the other pair helped when there were disagreements (BM). This systematic review was registered in PROSPERO (International Prospective Register of Systematic Reviews) in October 2022, with registration number CRD42022355721, and published at medRxiv 2024.02.29.24303561; do: https://doi.org/10.1101/2024.02.29.24303561
Electronic searches were performed in MEDLINE (via PubMed), LILACS (BVS), Cochrane Library, and Google Scholar, in addition to manual searches in the references of included studies and in non-indexed records. The following descriptors were used: The search will be done by the following terms (children) OR (Child) OR (Preschool) OR (Adolescents) OR (Adolescence) OR (Teens) OR (Teen) OR (Teenagers) OR (Teenager) OR (Youth) OR (Youths) OR (Adolescents, Female) OR (Adolescent, Female) OR (Female Adolescent) OR (Female Adolescents) OR (Adolescents, Male) OR (Adolescent, Male) OR (Male Adolescent) OR (Male Adolescents) AND (Exercises) OR (Physical Activity) OR (Activities, Physical) OR (Activity, Physical) OR (Physical Activities) OR (Exercise, Physical) OR (Exercises, Physical) OR (Physical Exercise) OR (Physical Exercises) OR (Acute Exercise) OR (Acute Exercises) OR (Exercise, Acute) OR (Exercises, Acute) OR (Exercise, Isometric) OR (Exercises, Isometric) OR (Isometric Exercises) OR (Isometric Exercise) OR (Exercise, Aerobic) OR (Aerobic Exercise) OR (Aerobic Exercises) OR (Exercises, Aerobic) OR (Exercise Training) OR (Exercise Trainings) OR (Training, Exercise) OR (Trainings, Exercise) AND (obesity) OR (Obesity, Abdominal) OR (Obesity, Maternal) OR (Obesity, Metabolically Benign) OR (Obesity, Morbid) OR (Pediatric Obesity) AND (interleukin -10) OR (Interleukin 10) OR (IL10) OR (IL-10) OR (CSIF-10) OR (Cytokine Synthesis Inhibitory Factor).
Inclusion and exclusion criteria are as follows the acronym “PICO” was used to assess study eligibility criteria. (P) participants: children and adolescents, (I) Intervention: Physical Activity, (C) Control: (obesity), (O) outcome: serum interleukin-10 levels. Articles published until February 2023 were included. Studies that were not available in full in any database and that were not found after attempts to contact the authors were excluded, as well as articles published in non-roman characters.
We assessed the quality of all included observational studies by outcomes using:
ROBINS-E. https://www.riskofbias.info/-. We assessed the quality of the included clinical trials using the Cochrane Risk of Bias tool, version 1 (Higgins et al., 2023).
Figure 1. Prisma Flow.
RESULTS AND DISCUSSIONS
The search strategy identified 378 citations. Following duplicate removal, we screened a total of 370 citations. We also screened 08 citations from the grey literature and three articles based on the opinions of experts and senior authors, of which 06 were potentially eligible.
Description of included studies.
Six studies were included in this review (Romeo J. et al., 2011; Duran et al., 2015; W.A. Lopes et al., 2016; Borfe L. et al., 2021; Rosa J.S. et al., 2011; Remmel et al., 2017) with a cross-sectional design, totaling 232 participants. In this first group, 6 studies were allocated, totaling 232 participants, aged between 9 and 16 years (12.84), these studies were carried out in Spain, the United States, Estonia, and Brazil, and they stratified the levels of physical activity practice, body mass index and Interleukin-10, with other results (Table 1).
These studies recruited children and adolescents from schools so that all participants were regularly enrolled. The study by (Romeo J. et al., 2011; and Remmel et al., 2017) was carried out on the European continent (Spain and Estonia respectively), respectively the study by (Duran et al., 2015 and Rosa J.S. et al., 2011) took place in the United States of America (W.A. Lopes et al., 2016; Borfe L. et al., 2021) was carried out in Brazil. To define the body mass index (BMI) (Romeo J. et al., 2011; Duran et al., 2015; W.A. Lopes et al., 2016; Borfe L. et al., 2021; Rosa J.S. et al., 2011), the calculation (kg/Height 2) was used, in studies by (Remmel et al., 2017; Duran et al., 2015; W.A. Lopes et al., 2016) body mass index was calculated with the aid from Total body scans were evaluated using dual-energy X-ray absorptiometry (DXA).
Table 01. Summary of results of the included studies in the primary analysis per outcome.
Physical activity
The Six studies, with 232 participants, aged between 9 and 16 years (12.84). The studies were carried out respectively on the following continents: North America (United States) Europe (Spain and Estonia) and South America (Brazil). In the study by (Duran et al., 2015 and Rosa J.S. et al., 2011), the ergometer cycle was used to calculate physical activity and daily minutes spent on physical activities. Describing an average of 20 to 30 (24.2) minutes of physical activity per day. In the studies by Remmel et al., (2017) and Romeo J. et al., (2011) accelerometers and Fitnessgran tests validated for the European population were used respectively, on the practice of physical activity, recording an average of 60 minutes of daily exercise. vigorous physical activity.
Brazilian findings for analyzing levels of physical activity practice (W.A. Lopes et al., 2016; Borfe L. et al., 2021) used (Polar Cardiac Monitor-FT1®, Finland), record an average of 60 minutes at the frequency of three times a week (table 1).
This systematic review reveals robust evidence of a positive association between serum levels of interleukin-10 pg/ml and increased body mass index (obesity) and levels of physical activity (Romeo J. et al., 2011; W.A. Lopes et al., 2016; Rosa J.S. et al., 2011). Physical activity is any movement of the body produced by skeletal muscles that results in greater energy expenditure than resting levels. Practicing physical activity outdoors, with sun exposure, would bring benefits both from the physical work itself and from the synthesis and action of vitamin D in the body (Mori et al., 2022).
In a systematic review, there was a tendency for us to present higher levels of interleukin-10 when associated with physical activity (Roth et al., 2018). Practicing physical activity provides better neuromuscular performance, including an increase in type II muscle fibers, and also improves the regulatory role of the immune system (Bouillon and Carmeliet, 2018).
Physical fitness and physical activity are inversely associated with cardiometabolic risk in adolescents (Husøy A., et al., 2021; Ortega F.B. et al., 2018). Likewise, physical fitness may attenuate the adverse association between high body weight/adiposity and cardiometabolic risk in children and adolescents.
Quality of assessment
The results of the assessment of the methodological quality of each included trial are in Figure 2.
Figure 2. The results of the assessment of the methodological quality of each included trial.
Three studies were considered to be at high risk of bias, primarily due to failure to report adequate methods of random sequence generation, allocation concealment, and failure to blind assessors (W.A. Lopes et al., 2016; Duran et al., 2015; Rosa J.S. et al., 2011).
Interleukin 10
In a study by Romeo J. et al., (2011) they found an association between body mass index and outdoor physical activity in Hispanics. Among Hispanics, there was a high prevalence of obese people compared to non-obese people when related to physical activity and Interleukin-10 indices after completing the program (before 17.6 ± 9.0 and after 13.4 ± 6.7) (Muscogiuri et al., 2017).
In the findings of Rosa J.S. et al., (2011) Il-10 levels were shown to be higher after 30 minutes of physical activity in obese children and adolescents. This trend was also found in the study by Duran et al, (2015).
Abdelhamid et al,(2020) also demonstrated that overweight and obese diabetic children had lower levels of IL-10 than non-obese diabetic children. Lauridsen et al., 2017, stated that downregulation of the mRNA expression of the anti-inflammatory cytokine IL-10 occurred with a gradual increase in BMI. Abnormal low IL-10 concentrations associated with autoimmune and inflammatory diseases were reported by Yao et al., (2013) Another study by Kupèa et al., (2021) reported that elevated IL-10 levels were observed in obese children and adolescents. These discrepancies may be explained because IL-10 may play a dual role in inflammation.
CONCLUSION
Vigorous physical activity has been recommended to control body mass index and metabolic changes. Obesity itself is one of the health indicators that modulate the innate immune system, increasing the release of pro-inflammatory cytokines from Th1 cells.
In the present study, we observed that the serum level of IL-10 correlated positively with the level of physical activity. More studies are needed to investigate the role of this biomarker in obesity. This finding reinforces the importance of encouraging physical activity and highlights the need to evaluate IL-10 levels in obese children and adolescents.
STUDY LIMITATIONS
The present study is limited to investigating the relationship between the effectiveness of physical activity in obese children and adolescents and serum levels of interleukin-10; therefore, other problems related to obesity were not the subject of this study. Another limitation of this study is that only two of the studies had group control. Therefore, our systematic review was performed without comparison with another group. For more robust results, controlled studies are needed.
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1 Discente do Curso Superior de Fisioterapia do Instituto de Saúde e Biotecnologia-ISB/UFAM e-mail: andrezapascoal@gmail.com; paula.sm372@gmail.com; lainarapessoa63@gmail.com
2 Docente do Curso Superior de Nutrição da Faculdade Metropolitana de Manaus (FAMETRO) Mestre em Ciências da Saúde (PPCIS/UFAM). e-mail: eduardordgznutri@gmail.com
3 Docente do Curso Superior Fisioterapia do Instituto de Saúde e Biotecnologia-ISB/UFAM Doutor em Imunologia Básica e Aplicada (PPGIBA/UFAM). e-mail: brunomori@ufam.edu.br