Underlying Mechanisms behind the Brain-Gut-Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update.

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain-gut-liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain-gut-liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

Negligible role for pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) in the nasopharyngeal colonization of mice with a serotype 6B pneumococcal strain.

Streptococcus pneumoniae colonizes the human nasopharynx asymptomatically, but it can also cause several diseases, including otitis media, pneumonia, bacteremia, and meningitis. The colonization of the nasopharynx by the bacteria is an essential step for the pneumococcus to invade other sites and cause diseases. Pneumococcal surface protein A (PspA) and Pneumococcal surface Protein C (PspC) are important virulence factors and have been described to play roles in adhesion and immune evasion. In this study, we immunized mice subcutaneously with the recombinant α-helical region of PspA and/or PspC combined with different adjuvants to assess protection against colonization with the serotype 6B strain BHN418. Though high serum levels of specific IgG were detected, none of the formulations led to reduction in the colonization of the nasopharynx. The negative result may be due to the poor induction of IgG2c, which has been previously correlated with protection against pneumococcal colonization in mice. Furthermore, BHN418 pspA and pspC single and double knockouts were evaluated in colonization experiments and no differences in bacterial load were observed. In competition assays with the wild-type strain, borderline to no reduction was observed in the loads of the knockouts. Our results contrast with data from the literature using other pneumococcal strains, showing that the role of PspA and PspC in colonization can vary depending on the background of the knockout strain studied. BHN418 has been selected for its capacity to colonize humans in experimental challenge studies and may have redundant factors that compensate for the lack of PspA and PspC during nasopharyngeal colonization of mice.

d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II.

BACKGROUND: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-ß-cyclodextrin (HßDL) during treatment with Doxo, focusing on the arrhythmic feature. METHODS: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HßDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. RESULTS: Electrocardiograms showed that administration of 10 mg/kg of HßDL prevented Doxo-induced widening of the QRS complex and QT interval. HßDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. CONCLUSION: Our results show that 10 mg/kg of ßDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation.

Garlic: A systematic review of the effects on cardiovascular diseases.

Allium sativum (garlic) certainly is one of the oldest horticultural crops in the world and presents bioactive compounds that are related to the garlic's effects on human health. Several authors have shown beneficial effects on diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases (CVD), which are among the most relevant causes of mortality in the world. The aim of this systematic review was to evaluate the effects of garlic in the risk factors of CVD and evaluate its economic importance. MEDLINE-PubMed, COCHRANE, EMBASE, and Google Scholar databases were searched. The included studies showed that the use of garlic can reduce blood pressure, waist circumference, body mass index, LDL-c, non-HDL-c, total cholesterol, triglycerides, and inflammatory markers. It also can increase the levels of HDL-c and can improve cardiovascular parameters such as coronary artery calcium, microcirculation, epicardial and periaortic adipose tissue, post occlusive reactive hyperemia, low attenuation plaque, carotid intima-media thickness; and carotid intima-media thickness. Due to these reasons, garlic can be considered in the prevention and treatment of CVD risk factors.

Effects of Vitamin D Supplementation in Diabetic Kidney Disease: An Systematic Review.

Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.

Curcumin, autoimmune and inflammatory diseases: going beyond conventional therapy - a systematic review.

Autoimmune and inflammatory diseases affect innumerous people and are considered a significant cause of morbidity and mortality worldwide and Curcuma sp can work as important therapies in the approach of these diseases. For this reason the aim of this review is to evaluate the effects of Curcuma or curcumin in five autoimmune and/or inflammatory diseases for instance, Inflammatory Bowel Disease, Osteoarthritis, Systemic Lupus Erythematous, Psoriasis, and Sclerosis. MEDLINE, EMBASE, and Cochrane Library were searched and PRISMA guidelines were used to build this systematic review. Curcuma sp or curcumin have been gaining ground in the treatment of autoimmune and inflammatory diseases due to the wide range of bioactive compounds capable of exerting substantial anti-inflammatory and antioxidant actions. The effects can be associated with improvement of symptoms and induction of remission in Inflammatory Bowel Disease patients; reduction of erythema and induration of lesions in psoriasis; and slow down the disease progression in patients with sclerosis. Furthermore, curcumin shows effects equivalent to ibuprofen and diclofenac, without the adverse effects generally reported by patients. Curcuma or its derivatives can be used safely and efficiently as adjuvants or as a main therapy for these diseases that increase year by year in the world population.

Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

The use of vitamin D for patients with inflammatory bowel diseases.

As Vitamin D (VD) plays an essential role in Inflammatory Bowel Diseases, this systematic review aimed to update the participation of this vitamin in the prevention or remission of these diseases. This review has included studies in MEDLINE-PubMed, EMBASE, and Cochrane databases. The authors have followed PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) guidelines. According to the inclusion and exclusion criteria, twenty-two randomized clinical trials were selected. In all, 1,209 patients were included in this systematic review: 1034 received only VD and 175 received VD in combination with calcium. The average doses of VD supplementation were from oral 400 IU daily to 10,000 IU per kilogram of body weight. Single injection of 300,000 IU of VD was also used. Several studies have shown the crucial role that VD plays in the therapeutic approach of IBD due to its effects on the immune system. It effectively decreased inflammatory cytokines such as TNF-α and IFN-γ (p<0.05) and provided a reduction in disease activity assessed through different scores such as Crohn's Disease Activity Index (CDAI) (p<0.05) and Ulcerative Colitis Disease Activity Index (UCDAI) (p<0.05). Unfortunately, the available clinical trials do not have standardization of doses and routes of administration. Existing meta-analyses are biased because they compare studies using different doses or treatments in combination with different drugs or supplements such as calcium. Even though VD has crucial effects on inflammatory processes, there is still a need for standardized studies to establish how the supplementation should be performed and the doses to be administered.

Organokines in Rheumatoid Arthritis: A Critical Review.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects the joints. Organokines can produce beneficial or harmful effects in this condition. Among RA patients, organokines have been associated with increased inflammation and cartilage degradation due to augmented cytokines and metalloproteinases production, respectively. This study aimed to perform a review to investigate the role of adipokines, osteokines, myokines, and hepatokines on RA progression. PubMed, Embase, Google Scholar, and Cochrane were searched, and 18 studies were selected, comprising more than 17,000 RA patients. Changes in the pattern of organokines secretion were identified, and these could directly or indirectly contribute to aggravating RA, promoting articular alterations, and predicting the disease activity. In addition, organokines have been implicated in higher radiographic damage, immune dysregulation, and angiogenesis. These can also act as RA potent regulators of cells proliferation, differentiation, and apoptosis, controlling osteoclasts, chondrocytes, and fibroblasts as well as immune cells chemotaxis to RA sites. Although much is already known, much more is still unknown, principally about the roles of organokines in the occurrence of RA extra-articular manifestations.

GLP-1a: Going beyond Traditional Use.

Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The objective of this study was to perform a systematic review on the use of GLP-1 other than in treating diabetes. PubMed, Cochrane, and Embase were searched, and the PRISMA guidelines were followed. Nineteen clinical studies were selected. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson's Disease and improve emotional well-being. In Alzheimer's disease, GLP-1 analogs can improve the brain's glucose metabolism by improving glucose transport across the blood-brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain's reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.

Organokines, Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise.

Sarcopenia is a disease that becomes more prevalent as the population ages, since it is directly linked to the process of senility, which courses with muscle atrophy and loss of muscle strength. Over time, sarcopenia is linked to obesity, being known as sarcopenic obesity, and leads to other metabolic changes. At the molecular level, organokines act on different tissues and can improve or harm sarcopenia. It all depends on their production process, which is associated with factors such as physical exercise, the aging process, and metabolic diseases. Because of the seriousness of these repercussions, the aim of this literature review is to conduct a review on the relationship between organokines, sarcopenia, diabetes, and other metabolic repercussions, as well the role of physical exercise. To build this review, PubMed-Medline, Embase, and COCHRANE databases were searched, and only studies written in English were included. It was observed that myokines, adipokines, hepatokines, and osteokines had direct impacts on the pathophysiology of sarcopenia and its metabolic repercussions. Therefore, knowing how organokines act is very important to know their impacts on age, disease prevention, and how they can be related to the prevention of muscle loss.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Antibacterial and modulatory activities of ß-cyclodextrin complexed with (+)-ß-citronellol against multidrug-resistant strains.

The present study aimed to investigate the antibacterial and modulatory activities of (+)-ß-citronellol (ßCT), ß-cyclodextrin (ß-CD), and their complex ßCT/ß-CD and characterize them using infrared spectroscopy. Infrared spectra were recorded in the 750-4000 cm-1 region. The antibacterial effects of these compounds and their modulatory-antibiotic activities were determined using the minimum inhibitory concentration (MIC) test. Signatures of these pure compounds were detected in the infrared spectrum of the ßCT/ß-CD complex. The MIC of the ßCT/ß-CD complex against the tested strains was found to be 1024 µg/mL. The antagonistic and synergistic effects of these compounds were also observed using the modulation tests. ßCT or ß-CD alone did not exhibit any direct antibacterial activity. However, the ßCT/ß-CD complex in combination with gentamicin showed a synergistic effect against E. coli.

Seroprevalence of SARS-CoV-2 antibodies in the poorest region of Brazil: results from a population-based study.

Population-based seroprevalence studies on coronavirus disease 2019 (COVID-19) in low- and middle-income countries are lacking. We investigated the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies in Sergipe state, Northeast Brazil, using rapid IgM-IgG antibody test and fluorescence immunoassay. The seroprevalence was 9.3% (95% CI 8.5-10.1), 10.2% (95% CI 9.2-11.3) for women and 7.9% (IC 95% 6.8-9.1) for men (P = 0.004). We found a decline in the prevalence of SARS-CoV-2 antibodies according to age, but the differences were not statistically significant: 0-19 years (9.9%; 95% CI 7.8-12.5), 20-59 years (9.3%; 95% CI 8.4-10.3) and ≥60 years (9.0%; 95% CI 7.5-10.8) (P = 0.517). The metropolitan area had a higher seroprevalence (11.7%, 95% CI 10.3-13.2) than outside municipalities (8.0%, 95% CI 7.2-8.9) (P < 0.001). These findings highlight the importance of serosurveillance to estimate the real impact of the COVID-19 outbreak and thereby provide data to better understand the spread of the virus, as well as providing information to guide stay-at-home measures and other policies. In addition, these results may be useful as basic data to follow the progress of COVID-19 outbreak as social restriction initiatives start to be relaxed in Brazil.

COVID-19 mortality among Indigenous people in Brazil: a nationwide register-based study.

Coronavirus disease 2019 (COVID-19) has disproportionately affected Black people and minority ethnic groups, but there are limited data regarding the impact of disease on Indigenous people. Herein, we investigated the burden of COVID-19 on the Indigenous population in Brazil. We performed a populational-based study including all cases and deaths from COVID-19 among Brazilian Indigenous people from 26 February to 28 August 2020. Data were obtained from official Brazilian information systems. We calculated incidence, mortality and fatality rates for the Indigenous population for each of the five Brazilian regions. Brazil had an incidence and a mortality rate of 3546.4 cases and 65.0 deaths per 100 000 population, respectively. The case fatality rate (CFR) was 1.8%. The Central-West had the higher estimates of disease burden among Brazilian Indians (incidence rate: 3135.0/100 000; mortality rate: 101.2/100 000 and CFR: 3.2%) followed by the North region (incidence rate: 5664.4/100 000; mortality rate: 92.2/100 000 and CFR: 1.6%). Governmental actions should guarantee the isolation, monitoring and testing capabilities of Indigenous people and rapidly to provide social protection and health facilities.

A systematic review of the antidepressant effects of curcumin: Beyond monoamines theory.

BACKGROUND: Depression is a severe, chronic, and recurring mental health disorder, which prevalence and morbimortality have increased in recent years. Several theories are proposed to elucidate the mechanisms of depression, such as the involvement of inflammation and the release of cytokines. Alternative treatments have been developed to improve outcomes of the commonly used drugs, and the use of Curcuma longa stands out. Its primary compound is named curcumin that exhibits antioxidant and anti-inflammatory effects. AIMS: Several studies have shown that curcumin may play antidepressant actions and, therefore, this study aimed to perform a systematic review of the antidepressant effects of curcumin to evaluate the impact of this compound in the treatment of this condition. METHODS: This systematic review has included studies available in MEDLINE-PubMed, EMBASE, and Cochrane databases, and the final selection included 10 randomized clinical trials. CONCLUSION: Curcumin improves depressant and anxiety behavior in humans. It can increase monoamines and brain-derived neurotrophic factor levels and may inhibit the production of pro-inflammatory cytokines and neuronal apoptosis in the brain. Systemically, curcumin enhanced insulin sensitivity, reduced cortisol levels, and reversed metabolic abnormalities. Studies with larger samples and standardized dose and formulation are required to demonstrate the benefits of curcumin in depression treatment since there are many variations in this compound's use.

Reduced cutaneous inflammation associated with antioxidant action after topical application of the aqueous extract of Annona muricata leaves.

Annona muricata L. is used in folk medicine for treatment of diseases related to inflammatory and oxidative processes. This study investigated the effect of the aqueous extract of A. muricata leaves (AEAM) on TPA-induced ear inflammation and antioxidant capacity, both in vitro and in vivo. The in vitro antioxidant capacity of AEAM was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing/antioxidant power (FRAP) and lipoperoxidation assays. Cytotoxicity and reactive oxygen species (ROS) release were evaluated in the L929 fibroblasts. Swiss mice were submitted to TPA application and were topically treated with AEAM (0.3, 1 or 3 mg/ear). After 6 h, inflammatory and oxidative parameters were evaluated. Quercetin 3-glucoside, rutin, chlorogenic acid, catechin and gallic acid were identified in AEAM. It also presented antioxidant activity in all in vitro assays used. Incubation with AEAM did not cause cell cytotoxicity but reduced ROS release from fibroblasts. Compared with the control group, treatment with AEAM significantly reduced ear oedema and mieloperoxidase activity in inflamed ears, as well as histological parameters of inflammation. These results were associated with the reduction of total hydroperoxides and modulation of catalase, but not superoxide dismutase activity. These findings show the anti-inflammatory effect of AEAM is associated with antioxidant capacity.

Effectiveness of Ozone Therapy as an Adjunct Treatment for Lower-Limb Ulcers: A Systematic Review.

OBJECTIVE: To evaluate the effectiveness of topical ozone therapy as an adjuvant treatment in the healing of lower limb ulcers through a systematic literature review. DATA SOURCES: Three databases were used to search for studies conducted in the period up to and including September 2020: PubMed, Scopus, and the Web of Science. STUDY SELECTION: The search identified 44 studies, 7 of which met the eligibility criteria and were evaluated. DATA EXTRACTION: Study design, study location, number of patients, patient age, type of control, wound type, intervention type, equipment used to generate ozone (ozone generation), evaluation methodology, and main results were extracted from each study. DATA SYNTHESIS: A total of 506 patients 18 years or older with chronic wounds, such as venous or diabetic ulcers, on the lower limbs were enrolled. The majority of studies addressed diabetic foot ulcers. CONCLUSIONS: The ozone therapy protocols demonstrated a healing effect in all included studies, and none reported adverse effects. This reinforces the need for more controlled and randomized clinical trials to determine the effectiveness of this treatment and establish clinical criteria for its use.

Smart Dressings for Wound Healing: A Review.

OBJECTIVE: To provide an overview of sensors incorporated into wound dressings that can be used to assess and manage healing parameters. DATA SOURCES: Authors conducted an extensive literature search of the Science Direct, Scopus, MEDLINE-PubMed, and Web of Science databases. STUDY SELECTION: A total of 587 studies that evaluated dressings used to manage wound healing parameters were identified in the search, but only 16 met all of the review criteria and were included in the final analysis. DATA EXTRACTION: Chronic wounds were the most common type of injury among studies. Six articles involved a wireless transmission system. DATA SYNTHESIS: All studies evaluated the physical and chemical characteristics of the dressings. CONCLUSIONS: This review demonstrates the lack of studies examining wound dressing sensors. New studies are required to assess sensors that allow not only wound monitoring, but also the application of drugs in a single dressing, providing a better and more cost-effective treatment for wounds.

Inflammatory modulation of fluoxetine use in patients with depression: A systematic review and meta-analysis.

There is growing evidence that there is a relationship between major depressive disorder (MDD), also simply known as "depression", and inflammatory processes. Selective serotonin inhibitors, such as fluoxetine, are used as a first-line treatment for depression, and it is hypothesized that its use can reduce levels of proinflammatory cytokines. The aim of this systematic review and meta-analysis is to enable a better understanding of how treatment with the antidepressant fluoxetine modulates inflammation, and the roles of the main cytokines in this process. Risk of bias (RoB) in the included studies was assessed using the Cochrane Risk of Bias Assessment tool for Non-randomized studies (RoBANS). In the meta-analysis, standardized mean difference (SMD) was used as a summary statistic and grouped statistics using the generic inverse variation method in RevMan 5 with random effects model. Heterogeneous changes in cytokine levels were also evaluated from the SMD forest plot of individual studies. After analysis, we observed that fluoxetine was able to decrease TNF-α levels (SMD ± 0.90, 95% CI = 0.16, 1.165, Z ± 2.40, p = 0.02), but not change IL-6 levels (SMD ± 0.37, 95% CI = 0.21, 0.95, Z ± 1.25, p = 0.21).Fluoxetine acts by modulating neuroimmunology, and not only by acting only on the independent restoration of neurotransmission and neuroinflammation pathways.