Immunomodulatory Medicines Research Articles

INVESTIGATING THE EFFECTS OF PAUSINYSTALIA YOHIMBE AQUEOUS LEAVES EXTRACT ON PARAMETERS FOR REPRODUCTIVE PERFORMANCE IN EXPERIMENTAL RATS

ABSTRACT BACKGROUND: Herbal plants and herbal preparations are widely used as immunomodulatory medicines that helps in improving reproductive health in humankind, and they are globally used and have rapidly grown in economic developmental importance. OBJECTIVE: The study was conducted to investigate the effects of the aqueous extract of P. yohimbe leaves on sexual reproductive performance in Wistar rats. The primary outcome of the study is the reproductive performance sexual rate. METHODS: The experimental study was carried out on albino rats of the Wistar strain, weighing between 150 and 200g sexually naive. The animals were raised in polyethylene cages and divided into four groups, which received a saline solution (control group), 2, 5, and 10 mL/kg of the aqueous extract of P. yohimbe leaves for fourteen days orally. The sexual behavior test was performed according to three types of crossing. RESULTS: The results of the treated groups showed a significant increase in mating frequency compared to the control group. Overall, the results showed that P. yohimbe significantly affects sexual behavior. The aqueous extract of P. yohimbe leaves increased sexual behaviour and orientation activity performance recorded in the treated rats. CONCLUSION AND RECOMMENDATION: The enhanced reproductive performance appetitive detected in the study, justify the indigenous use of the herbal plant in reproductive medicine and could be a precursor in the synthesis of useful drugs. However, based on the current findings, we recommend that careful administration be considered as a better option justifying human circumstances for patient with advanced mankind age in low dosage resource settings, as it achieves a better reproductive performance rate at a lower dose dependent increase.

Plant-derived bioactive compounds as key players in the modulation of immune-related conditions

AbstractThe immune system is a complex and fundamental network for organism protection. A minimal unbalance in the host defense system homeostasis can originate severe repercussions in human health. Fundamentally, immune-related diseases can arise from its compromise (immunodeficiency diseases), overactivation against itself (autoimmune diseases) or harmless substances (allergies), and failure of eliminating the harmful agent (chronic inflammation). The notable advances and achievements in the immune system diseases pathophysiology have been allowing for a dramatic improvement of the available treatments. Nevertheless, they present some drawbacks, including the inappropriate benefit/risk ratio. Therefore, there is a strong and urgent need to develop effective therapeutic strategies. Nature is a valuable source of bioactive compounds that can be explored for the development of new drugs. Particularly, plants produce a broad spectrum of secondary metabolites that can be potential prototypes for innovative therapeutic agents. This review describes the immune system and the inflammatory response and examines the current knowledge of eight plants traditionally used as immunomodulatory medicines (Boswellia serrata, Echinacea purpurea, Laurus nobilis, Lavandula angustifolia, Olea europaea, Salvia officinalis, Salvia rosmarinus, and Taraxacum officinale). Moreover, the issues responsible for possible biologic readout inconsistencies (plant species, age, selected organ, developmental stage, growth conditions, geographical location, drying methods, storage conditions, solvent of extraction, and extraction method) will also be discussed. Furthermore, a detailed list of the chemical composition and the immunomodulatory mechanism of action of the bioactive compounds of the selected plant extracts are presented. This review also includes future perspectives and proposes potential new avenues for further investigation.

Self-assembled adipose-derived mesenchymal stem cells as an extracellular matrix component- and growth factor-enriched filler.

The clinical application of mesenchymal stem cells (MSCs) is attracting attention due to their excellent safety, convenient acquisition, multipotency, and trophic activity. The clinical effectiveness of transplanted MSCs is well-known in regenerative and immunomodulatory medicine, but there is a demand for their improved viability and regenerative function after transplantation. In this study, we isolated MSCs from adipose tissue from three human donors and generated uniformly sized MSC spheroids (∼100µm in diameter) called microblocks (MiBs) for dermal reconstitution. The viability and MSC marker expression of MSCs in MiBs were similar to those of monolayer MSCs. Compared with monolayer MSCs, MiBs produced more extracellular matrix (ECM) components, including type I collagen, fibronectin, and hyaluronic acid, and growth factors such as vascular endothelial growth factor and hepatocyte growth factor. Subcutaneously injected MiBs showed skin volume retaining capacity in mice. These results indicate that MiBs could be applied as regenerative medicine for skin conditions such as atrophic scar by having high ECM and bioactive factor expression.

A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases

Background There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. Methods We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. Results 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24–1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005–2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. Conclusions The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not. KEY MESSAGES What is already known? o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual’s risk of inflammatory and autoimmune disease (IAD). What is new here? o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy. How can this study help patient care? o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

Bioinformatic approach for repurposing immunomodulatory drugs for lepromatous leprosy.

The lepromatous leprosy (LL) disease is caused by Mycobacterium leprae and Mycobacterium lepromatosis which is characterized by inadequate response to treatment, a propensity to drug resistance, and patient disability. We aimed to evaluate current immunomodulatory medicines and their target proteins collectively as a drug repurposing strategy to decipher novel uses for LL. A dataset of human genes associated with LL-immune response was retrieved from public health genomic databases including the Human Genome Epidemiology Navigator and DisGeNET. Retrieved genes were filtered and enriched to set a robust network (≥10, up to 21 edges) and analyzed in the Cytoscape program (v3.9). Drug associations were obtained in the NDEx Integrated Query (v1.3.1) coupled with drug databases such as ChEMBL, BioGRID, and DrugBank. These networks were analyzed in Cytoscape with the CyNDEx-2 plugin and STRING protein network database. Pathways analyses resulted in 100 candidate drugs organized into pharmacological groups with similar targets and filtered on 54 different drugs. Gene-target network analysis showed that the main druggable targets associated with LL were tumoral necrosis factor-alpha, interleukin-1B, and interferon-gamma. Consistently, glucosamine, binimetinib, talmapimod, dilmapimod, andrographolide, and VX-702 might have a possible beneficial effect coupled with LL treatment. Based on our drug repurposing analysis, immunomodulatory drugs might have a promising potential to be explored further as therapeutic options or to alleviate symptoms in LL patients.

Extracellular vesicle-mediated drug resistance in multiple myeloma

Because of innovative therapeutic agents such as proteasome inhibitors, immunomodulatory medicines, and antibody medications, the prognosis of multiple myeloma (MM) has considerably improved in recent years. However, the prognosis for MM patients with treatment resistance and extramedullary illness remains poor. The interaction between MM cells and their surrounding cells in the bone marrow microenvironment is critical for medication resistance development. Many issues cannot be explained by liquid factors, such as cytokines and chemokines. Extracellular vesicles (EVs) have gained interest due to their role in the advancement of several forms of cancers. In this article, we primarily summarize MM drug resistance and examine the most recent articles on small-EVs (particularly exosomes) that contribute to MM drug resistance acquisition.

On the Immunotherapy for Tumors

Tumor immunotherapy has made major strides in recent years, greatly enhancing the survival rate of cancer patients. Tumor vaccines, cellular immunotherapy, immunomodulatory medicines targeting T cells, immune checkpoint inhibitors (ICIs), and other forms of immunotherapy treatments have all developed one after the other. As new high-tech technologies emerge, tumor immunotherapy techniques are also continuously improved.

Astragalus polysaccharide: a review of its immunomodulatory effect.

The Astragalus polysaccharide is an important bioactive component derived from the dry root of Astragalus membranaceus. This review aims to provide a comprehensive overview of the research progress on the immunomodulatory effect of Astragalus polysaccharide and provide valuable reference information. We review the immunomodulatory effect of Astragalus polysaccharide on central and peripheral immune organs, including bone marrow, thymus, lymph nodes, spleen, and mucosal tissues. Furthermore, the immunomodulatory effect of Astragalus polysaccharide on a variety of immune cells is summarized. Studies have shown that Astragalus polysaccharide can promote the activities of macrophages, natural killer cells, dendritic cells, T lymphocytes, B lymphocytes and microglia and induce the expression of a variety of cytokines and chemokines. The immunomodulatory effect of Astragalus polysaccharide makes it promising for the treatment of many diseases, including cancer, infection, type 1 diabetes, asthma, and autoimmune disease. Among them, the anticancer effect is the most prominent. In short, Astragalus polysaccharide is a valuable immunomodulatory medicine, but further high-quality studies are warranted to corroborate its clinical efficacy.

A Novel Mechanism of Macrophage Activation by the Natural Yolkin Polypeptide Complex from Egg Yolk.

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-β and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.

Effects of ethanolic extract of the Cleome arabica on sexual behavior in Wistar rats

Traditional medicinal plants are widely used as immunomodulatory medicines that help improve health. A total of 50 plants used for the treatment of toxicity were screened for their protective effects. Traditional medicinal are globally used and have rapidly grown in economic importance. Intrinsically active compounds are well-known for their antioxidant, anti-tumor, anti-viral, and anti-inflammatory activities. The study was conducted to investigate the effects of the ethanolic extract of C. arabica leaves on sexual behavior in Wistar rats. C. arabica, a medicinal plant with a foul odor, toxic, and has hallucinogenic effects. The experimental study was carried out on white rats (male and female) of the Wistar strain from the Pasteur Institute of Algiers (Kouba, Algeria), weighing between 150 and 200g sexually naive. The animals were raised in polyethylene cages and divided into two groups (n = 10 rats/group), which received a saline solution (male and female control group), 0.20µg/ml of the ethanolic extract of C.arabica leaves for seven days orally (male and female treated group). The sexual behavior test was performed according to three types of crossing. The results of the treated groups showed a significant increase in mating frequency compared to the control group. Overall, the results showed that C. arabica significantly affects sexual behavior. The ethanolic extract of C. arabica increased sexual behavior and orientation activity performance recorded in the treated animals. Thus, this study found that C. arabica has a significant effect on the rats' sexual behavior.

Emerging Immunomodulatory Therapies and New Treatment Paradigms for Axial Spondyloarthritis.

The purpose of this review is to educate the reader about the evolving classification of axial spondyloarthritis (AxSpA) and describe recent treatment data from clinical trials of medications with mechanisms of action other than TNF inhibition. The review will also address emerging treatment strategies for AxSpA. New and more sensitive classification schema for AxSpA find that the prevalence of the disease is more than twice that of the historic definition of ankylosing spondylitis (AS), when patients without radiographically observable damage to the sacroiliac joints are included. TNF inhibitors have shown efficacy in the full spectrum of disease. IL-17 inhibitors, e.g., secukinumab and ixekizumab and janus kinase (JAK) inhibitors, have shown good efficacy and relatively good safety in radiographically defined AxSpA and are being tested in non-radiographic (nr) AxSpA. Several immunomodulatory medicines approved for psoriasis, psoriatic arthritis, and rheumatoid arthritis have not shown efficacy in AxSpA, highlighting the importance of conducting good-quality, placebo-controlled trials in this condition. Treatment strategies such as "treat to target" and tapering therapy are being studied. There remains a large unmet need to identify and adequately treat the full spectrum of AxSpA. The use of TNF inhibitors has improved our ability to achieve remission or low disease activity in AxSpA. Newer medicines with different mechanisms of action, e.g., IL-17 or JAK inhibition, are also showing similar ability. Continued research, including identification of new targets of treatment, is critical.

Advances in Research on Immunoregulation of Macrophages by Plant Polysaccharides.

Polysaccharides are among the most important members of the biopolymer family. They are natural macromolecules composed of monosaccharides. To date, more than 300 kinds of natural polysaccharide compounds have been identified. They are present in plants, animals, and microorganisms, and they engage in a variety of physiological functions. In the 1950s, due to the discovery of their immunoregulatory and anti-tumor activities, polysaccharides became a popular topic of research in pharmacology, especially in immunopharmacology. Plants are an important source of natural polysaccharides. Pharmacological and clinical studies have shown that plant polysaccharides have many functions, such as immune regulation, anti-tumor activity, anti-inflammatory activity, anti-viral functions, anti-radiation functions, and a hypoglycaemic effect. The immunomodulatory effects of plant polysaccharides have received much attention. Polysaccharides with these effects are also referred to as biological response modifiers (BRMs), and research on them is one of the most active areas of polysaccharide research. Thus, we summarize immunomodulatory effects of botanical polysaccharides isolated from different species of plants on the macrophage. The primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, including increasing reactive oxygen species (ROS) production, and enhancing secretion of cytokines and chemokines. Therefore, it is believed that botanical polysaccharides have significant therapeutic potential, and represent a new method for discovery and development of novel immunomodulatory medicine.

Pericytes in the Umbilical Cord.

The structural components of the umbilical cord, including two arteries and one vein, the stromal region/Wharton's jelly, and amniotic epithelial membrane, are well described at various time points of gestation. Over the last two decades, evidence has emerged that multipotent cells sharing properties of mesenchymal stromal cell and pericytes/mural cells can be isolated from multiple regions of the umbilical cord, including the perivascular region of the umbilical cord arteries and vein, Wharton's jelly, and subamnion. These cells have increasingly gained interest for their potential use in regenerative and immunomodulatory medicine. Recent studies suggest that obstetrical complications including gestational diabetes mellitus and preeclampsia may alter the yield, properties, and potency of mesenchymal stromal cells isolated from the umbilical cord. The role that pericytes or pericyte-like cells play in the development of the human umbilical cord and associated pathologies, however, remains to be investigated.

Antioxidant effects of immunomodulators in patients with recurrent pyelonephritis

The purpose of our work was to investigate the effect of immunomodulatory medicines on the intensity of oxidative stress (OS), the cytokines level and the activity of renospecific enzymes in patients with recurrent pyelonephritis (rPN).
 Methods. A prospective, randomized, open-label study involved of 100 women aged 33.4 ± 8.8 year old. According to the sensitivity of the detected pathogens all patients received antibacterial therapy for two weeks. Along with the main course of antibiotic therapy, 25 patients were assigned Sodium nucleinate at a dose of 0.25 g 4 times per day during 14 days, 18 patients were prescribed Galavit intramuscularly 2 ml per dayfor 10 days, and 27patients were prescribed Proteflazid according to the manufacturer’s instructions. The comparison group consisted of 30 women with rPN who received antibiotic therapy exclusively.Women were screened before and after the treatment. The content of malondialdehyde (MDA), ceruloplasmin (CP), transferrin (TF) and sulfhydryl groups (SH-groups) were determined in the blood by colorimetric method. Oxidative stress index (OSI) was calculated. The concentration of interleukins (IL) -1f, -4, -8, -10, -17, tumor necrosis factor a (TNF-a), transforming growth factor f (TGF-f), monocytic chemoactive protein-1 (MCP-1) and interferon y (IFN-y) were analyzed in the blood of the women using an ELISA. To evaluate the functional state of the renal parenchyma the activity of tubular lysosome enzymes a total f-N-acetylhexosaminidase and f-galactosidase were determined in urine.
 Results. The use of Sodium nucleinate decreased of the OS activity by reducing MDA level (p <0.001) and increasing the concentration of CP (p < 0.03). The serum levels ofIL-4 (p = 0.007), lL-17 (p = 0.04), TGF-f (p = 0.02) and MCP-1 (p = 0.03) were decrease. The use of Galavit contributed to a statistically significant decrease in the concentration of TNF-a (p <0.001), IL-8(p <0.001), IFN-y (p = 0.001) and TGF-f (p <0.001). The administration of Proteflazid resulted in a decrease in the concentrations of IL-8 and IFN-y, with a decrease in OSI (p =0.04) compared to pre-treatment. All applied immunomodulators partially reduced the activity of renospecific enzymes markers of kidney damage.
 Conclusions. The use of immunomodulators in the complex therapy of patients with rPN contributes to the partial normalization of functional activity of immune system by the decreasing ofthe production ofcytokines as its mediators and the reducing ofthe OS intensity.

Process signatures in glatiramer acetate synthesis: structural and functional relationships

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

Identification of the protective effects of traditional medicinal plants against SDS-induced Drosophila gut damage

Traditional medicinal plants are widely used as immunomodulatory medicines that help improve health. A total of 50 different plants used for the treatment of toxicity were screened for their in vivo protective effects. Flies were fed a standard cornmeal-yeast medium (control group) or the standard medium containing medicinal plant extracts (experimental groups). Assessment of the survival rate was performed by feeding flies with toxic compounds. Gut epithelial cells were analyzed for cell proliferation and death by green fluorescent protein antibodies and 7-aminoactinomycin D staining under the microscope. The expression of antimicrobial peptides (AMPs) was evaluated by the quantitative polymerase chain reaction and the results revealed that after feeding the flies with toxic compounds, aqueous extracts from Codonopsis pilosula (Franch.) Nannf (C. pilosula), Saussurea lappa (Decne.) C.B.Clarke (S. lappa), Imperata cylindrica Beauv.var.major (Nees) C.E. Hubb. (I. cylindrical var. major) and Melia toosendan Sied. Et Zucc. (M.toosendan) increased the fly survival rate, reduced epithelial cell death and improved gut morphology. In addition, C. pilosula extracts induced the antimicrobial peptide levels (Dpt and Mtk) following treatment with sodium dodecyl sulfate (SDS). However, these extracts were not observed to increase SDS-induced cell proliferation in vivo. These results indicate that there are strong protective effects in extracts of C. pilosula, S. lappa, I. cylindrical var. major and M. toosendan on Drosophila intestinal cells among 50 medicinal plants.

▼ Apremilast for psoriasis and psoriatic arthritis

▼ Apremilast (Otezla - Celgene Europe Ltd.) is a novel orally administered immunomodulatory medicine licensed for the treatment of plaque psoriasis and psoriatic arthritis.1 The company suggests that it has...

A Systematic Review of Drugs in Late-Stage Development for the Treatment of Multiple Sclerosis: A Focus on Oral Synthetic Drugs

Multiple sclerosis (MS) is a heterogeneous, chronic, debilitating immune-mediated disease of the central nervous system (CNS). There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). There is no definite cure for MS, thus medications typically focus on slowing the progression of the disease, managing symptoms and improving the quality of life. There is no specific medication for the management of PPMS and thus these patients are often neglected. New medicines in this phase of the disease are needed. On the other hand injectable immunomodulatory medicines, which dominated the MS market for over the past two decades, raise the issues of adherence and tolerance while oral therapies do offer a step forward in convenience. This systematic review article discusses the emerging synthetic small molecule that administered orally for MS treatment. We searched PubMed, Web of Science and Google Scholar to summaries the present knowledge on mechanism of action, and completed and current clinical trial of laquinimod, masitinib and siponimod. Data were collected from 1985 to January 2015. The development of effective medicines for MS is critically dependent upon understanding the biological basis of this complex multifactorial disease. The current pharmacotherapeuetic options for its treatment are mainly immunomodulators which were developed on the basis that MS is an autoimmune disease. The new synthetic small molecule agents such as laquinimod, masitinib and siponimod with different mechanism of actions can be administered orally rather than by injection.

New and emerging immune-targeted drugs for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered.

The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010

Background and purposeSystemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients.MethodWe measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone.ResultsOur present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD.ConclusionWhether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.