BACKGROUND: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.
METHODS: A systematic search was undertaken in PubMed, MEDLINE, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change.
RESULTS: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn.
CONCLUSIONS: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) β1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-β1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.

Interlukin-15 (IL-15) is an inflammatory cytokine that plays a vital role in immunology and obesity-associated metabolic syndrome. We performed this systematic review and meta-analysis to investigate whether exercise promotes circulating IL-15 concentrations in adults.
We searched PubMed, Web of Science, and Scopus from inception to May, 2023 and identified original studies that investigated the effectiveness of acute and/or chronic exercise on serum/plasma IL-15 levels in adults. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using random effect models. Subgroup analyses were performed based on type of exercise, and training status, health status and body mass indexes (BMI) of participants.
Fifteen studies involving 411 participants and 12 studies involving 899 participants were included in the acute and chronic exercise analyses, respectively. Our findings showed that acute exercise increased circulating IL-15 concentrations immediately after exercise compared with baseline [SMD=0.90 (95% CI: 0.47 to 1.32), p=0.001], regardless of exercise type and participants\' training status. Similarly, acute exercise was also associated with increased IL-15 concentrations even one-hour after exercise [SMD=0.50 (95% CI: 0.00 to 0.99), p=0.04]. Nevertheless, chronic exercise did not have a significant effect on IL-15 concentrations [SMD=0.40 (95% CI: -0.08 to 0.88), p=0.10].
Our results confirm that acute exercise is effective in increasing the IL-15 concentrations immediately and one-hour after exercise intervention, and thereby playing a potential role in improving metabolism in adults.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=445634, identifier CRD42023445634.

Celiac disease (CD) presents a complex interplay of both innate and adaptive immune responses that drive a variety of pathological manifestations. Recent studies highlight the role of immune-mediated pathogenesis, pinpointing the involvement of antibodies against tissue transglutaminases (TG2, TG3, TG6), specific HLA molecules (DQ2/8), and the regulatory role of interleukin-15, among other cellular and molecular pathways. These aspects illuminate the systemic nature of CD, reflecting its wide-reaching impact that extends beyond gastrointestinal symptoms to affect other physiological systems and giving rise to a range of pathological landscapes, including refractory CD (RCD) and, in severe cases, enteropathy-associated T cell lymphoma. The existing primary therapeutic strategy, a gluten-free diet (GFD), poses significant challenges, such as low adherence rates, necessitating alternative treatments. Emerging therapies target various stages of the disease pathology, from preventing immunogenic gluten peptide absorption to enhancing intestinal epithelial integrity and modulating the immune response, heralding potential breakthroughs in CD management. As the understanding of CD deepens, novel therapeutic avenues are emerging, paving the way for more effective and sophisticated treatment strategies with the aim of enhancing the quality of life of CD patients. This review aims to delineate the immunopathology of CD and exploring its implications on other systems, its complications and the development of novel treatments.

There is evidence that the adaptive or acquired immune system is one of the crucial variables in differentiating the course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work aimed to analyze the immunopathological aspects of adaptive immunity that are involved in the progression of this disease.
This is a systematic review based on articles that included experimental evidence from in vitro assays, cohort studies, reviews, cross-sectional and case-control studies from PubMed, SciELO, MEDLINE, and Lilacs databases in English, Portuguese, or Spanish between January 2020 and July 2022.
Fifty-six articles were finalized for this review. CD4+ T cells were the most resolutive in the health-disease process compared with B cells and CD8+ T lymphocytes. The predominant subpopulations of T helper lymphocytes (Th) in critically ill patients are Th1, Th2, Th17 (without their main characteristics) and regulatory T cells (Treg), while in mild cases there is an influx of Th1, Th2, Th17 and follicular T helper cells (Tfh). These cells are responsible for the secretion of cytokines, including interleukin (IL) - 6, IL-4, IL-10, IL-7, IL-22, IL-21, IL-15, IL-1α, IL-23, IL-5, IL-13, IL-2, IL-17, tumor necrosis factor alpha (TNF-α), CXC motivating ligand (CXCL) 8, CXCL9 and tumor growth factor beta (TGF-β), with the abovementioned first 8 inflammatory mediators related to clinical benefits, while the others to a poor prognosis. Some CD8+ T lymphocyte markers are associated with the severity of the disease, such as human leukocyte antigen (HLA-DR) and programmed cell death protein 1 (PD-1). Among the antibodies produced by SARS-CoV-2, Immunoglobulin (Ig) A stood out due to its potent release associated with a more severe clinical form.
It is concluded that through this study it is possible to have a brief overview of the main immunological biomarkers and their function during SARS-CoV-2 infection in particular cell types. In critically ill individuals, adaptive immunity is varied, aberrantly compromised, and late. In particular, the T-cell response is also an essential and necessary component in immunological memory and therefore should be addressed in vaccine formulation strategies.

The purpose of the study was to test the effect of ageing, BMI, physical activity and chronic exercise on IL-15 blood concentration by meta-analyses of the literature.
The search was performed on PubMed/MEDLINE, Web of Science, ProQuest, Embase and Cochrane databases. First meta-analysis compared blood IL-15 of healthy adults across three age groups (<35 years, 35-65 years, and >65 years), considering BMI as confounding factor; the second compared IL-15 levels between physically active and non-physically active individuals (cross-sectional studies); and the third tested the effect of chronic exercise interventions on blood IL-15 levels on participants of any age, sex, and health condition.
From 2582 studies retrieved, 67 were selected for the three meta-analyses (age effect: 59; physical activity cross-sectional effect: 5; chronic exercise effect: 14). Older adults had lower blood IL-15 than young and middle-aged adults (5.30 pg/ml [4.76; 5.83]; 7.11 pg/ml [6.33; 7.88]; 7.10 pg/ml [5.55; 8.65], respectively). However, the subgroup of overweight older adults had higher IL-15 than young and middle aged overweight adults; Habitual physical activity did not affect blood IL-15 (standardized mean difference [SMD] 0.61 [-0.65; 1.88], p = 0.34); Chronic exercise reduced blood IL-15 in short-term interventions (<16 weeks) (SMD -0.14 [-0.27; -0.01], p = 0.04), but not studies of >16 weeks of intervention (SMD 0.44 [-0.26; 1.15], p = 0.22).
The present meta-analyses highlight the complex interaction of age, BMI and physical activity on blood IL-15 and emphasize the need to take these factors into account when considering the role of this myokine in health throughout life.

Conducted studies highlight that a mixture of genetic and environmental factors is responsible for rheumatoid arthritis (RA) development. This study aimed to analyze the available literature for the relationship between, on the one hand, single-nucleotide polymorphisms (SNPs) in the proinflammatory cytokines genes interleukin-1 (IL-1), -6, -8, -15, -17, -18, and -23, and tumor necrosis factor-alpha (TNF-α), and on the other hand, RA susceptibility, severity, and patients\' response to applied treatment. The PubMed database was searched for sources. Preference was given to articles which were published within the past 20 years. Data indicate that the relationship between selected SNPs in proinflammatory cytokines genes and susceptibility to developing RA is inconclusive, and it depends on the ethnicity of the population. Although the allelic and genotypic frequencies of many SNPs in proinflammatory cytokines genes analyzed did not differ between RA patients and healthy controls, deeper analysis showed that these polymorphisms have a relationship with clinicopathological features of RA. SNPs in proinflammatory cytokines genes also \"modify patients\' response\" to applied treatment. Further studies, on larger cohorts of subjects and in different populations, should be conducted to elucidate the role of SNPs in IL-1, -6, -8, -15, -17, -18, and -23, and TNF-α genes in RA patients.

The immune system is dysfunctional in cancer, and therapeutic approaches designated to restore immunity and increase long-term overall survival are desirable. The role of immunotherapy is to trigger the immune system to recognize and destroy tumor cells. Interleukin-15 (IL-15) is a member of the common gamma-chain (γc) cytokines that promote the differentiation and expansion of T cells, B cells and natural killer (NK) cells, leading to enhanced antitumor responses. This suggests that IL-15 is a promising candidate for anticancer therapy. Renewed interest in cancer immunotherapy has led to an increased number of preclinical studies and clinical trials that have investigated the reliability and potency of IL-15-based agents, not only as single therapy, but also in combination with others. This review provides a description of these studies which show the advantages and disadvantages of IL-15 as an immunotherapeutic agent. We present here the role of IL-15 and pharmacologically improved IL-15 superagonists as a single treatment or in combination with other therapeutic agents.

Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.

The clinical validity and utility of complex biomarkers have not been extensively studied in bladder cancer. Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8 T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. Patients were tested before being treated under our expanded access protocol for intravesical BCG with ALT-803. Subject 1 had failed his fourth line of therapy, subject 2 had failed only his first line of therapy, and subject 3 had failed his seventh line of therapy. Surprisingly, subject 1 had an unusually prolonged CR which lasted 30 months; subject 2 had the persistent and recurrent disease until 12 months when he then developed a CR; subject 3 had disease recurrence at 3 months, along with progression noted at 6 months. Immunomutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for subject 1, who had an exceptional response. Compared with subject 3, tumor in subject 1 demonstrated a high level of expression for CTLA4 (immunosuppression) and CD39 (immunosuppressive). Together, an immunosuppressive tumor environment in nonmuscle invasive bladder cancer that have failed prior BCG may respond better to interleukin-15 immunotherapy compared with tumors without an immunosuppressive environment.