Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.
Animals ; Cytokines ; Interleukin-27 ; Autoimmune Diseases ; Arthritis, Rheumatoid ; Neoplasms

OBJECTIVE: To investigate the effect of IL-27 on Th17 cells in patients with henoch-schönlein purpura（HSP） in order to further elucidate the pathogenesis. METHODS: Fifty patients with HSP treated in our hospital from April 2019 to July 2019 were selected as HSP group, and 30 volunteers underwent physical examination at the same time were selected as control group. The proportion of Th17 cells in peripheral blood of HSP group and healthy control group was determined by flow cytometry (FCM). A total of 27 HSP patients were selected, and candidate peripheral blood mononuclear lymphocytes (PBMC) were co-cultured with exogenous rhIL-27, and the ratio of Th17 cells was detected by flow cytometry. RESULTS: The proportion of Th17 cells in the peripheral blood of HSP patients with acute phase was (1.57±0.54)%, which was significantly higher than that of the control group (0.86±0.40)% (t=-6.298, P<0.001), and the proportion of Th17 cells was decreased significantly after rhIL-27 co-culture (1.39%±0.52% vs 0.98%±0.44%)(P<0.05). CONCLUSION IL-27 can reduce the level of Th17 cells in patients with HSP, which may be involved in the pathogenic process of HSP and play a protective role in the development of the disease.
Humans ; Interleukin-27 ; Leukocytes, Mononuclear ; Patients ; Purpura, Schoenlein-Henoch ; Th17 Cells

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

As a member of IL-6/IL-12 cytokine family, IL-27 is a heterodimeric cytokine composed of the p28 and EBI3. Functioning as a linkage between innate and adaptive immunity, IL-27 is mainly produced by activated antigen-presenting cells and has a variety of responder cells including T cells, NK cells, macrophages and dendritic cells. IL-27 plays an antitumor role through promoting the production of cytotoxic T cells, regulating the differentiation of T cell subsets, enhancing the function of NK cells and inhibiting the angiogenesis. On the other hand, IL-27 may also have a positive effect on tumor progress and metastasis. IL-27 can be used as a reference marker for tumor diagnosis, due to its relation to the occurrence and development of tumors. This article reviews the research progress on the roles of IL-27 in tumor biological regulation.
Dendritic Cells ; Humans ; Interleukin-27 ; immunology ; Killer Cells, Natural ; Macrophages ; Neoplasms ; immunology ; T-Lymphocyte Subsets ; T-Lymphocytes, Cytotoxic

OBJECTIVEThis study aimed to conduct a preliminary study on the possible role and significance of interleukin (IL)-12 and IL-27 in the pathogeneses of oral lichen planus (OLP).

METHODSThirty cases of patients with OLP (fifteen cases of reticular OLP and fifteen cases of erosive OLP) were enrolled in this study, and twenty cases of healthy people served as controls. Lymphocyte subsets CD3+, CD4+, CD8+, CD19+, and CD16+56 [natural killer cell (NK)] were tested using flow cytometry, and humoral immunity [immunoglobulin (Ig)G, IgA, IgM, C3, C4] were examined using nephelometry assays. IL-12 and IL-27 contents in serum of patients with OLP and normal controls were detected through enzyme linked immunosorbent assay. The correlations between the levels of IL-12, IL-27, immune status, and clinical characteristics of patients with OLP were analyzed, respectively.

RESULTSCD3+, CD4+, and CD8+in patients with OLP were markedly lower than the normal value, whereas CD 19+ of OLP in patients was significantly higher than the normal value (P<0.05). IgM inpatients with OLP was increased, whereas C4 was declined (P<0.05). IL-12 and IL-27 levels showed significant upregulation or ULF patients compared with control groups (P<0.05). Meanwhile, positive correlations existed between IL-12 andIL-27 levels in the serum of patients with OLP (r=0.912, P<0.01). No significant correlations of IL-12 and IL-27 epressions with clinical characteristics of OLP were found (P>0.05). Negative correlations of IL-12 and IL-27 levels with CD16+56(NK) cells were observed (r1 = -0.416, P1 = 0.022; r2 = -0.392, P2=0.032, respectively), whereas a positive correlation existed for IgG (r1=0.445, P1=0.014; n=0.549, P2=0.002, respectively).

CONCLUSIONA cellular immune dysfunction mainly dominate in patients with OLP, accompanied by some degree of humoral-immunity-function disorder. The abnormally high expressions of IL-12 and IL-27 are possibly synergized and promoted inflammation development in OLP. Its promotion takes place through the negatie feedback regulation of humoral immune responses, which are involved in the regulation of immune mechanisms of OLP.

Flow Cytometry ; Humans ; Immunoglobulins ; blood ; Interleukin-12 ; blood ; Interleukin-12 Subunit p35 ; metabolism ; Interleukin-27 ; blood ; Interleukins ; metabolism ; Killer Cells, Natural ; Lichen Planus, Oral ; blood ; immunology

OBJECTIVEInterleukin-27 (IL-27) has been reported to reduce the levels of interleukin-17 (IL-17) and alleviate the severity of experimental autoimmune myocarditis. IL-17, an important tissue-protective cytokine in viral myocarditis (VMC), has been reported to increase synovial expression of IL-27 in rheumatoid arthritis. However, the influence of IL-17 on IL-27 expression in murine model of VMC remains unknown.

METHODSWild-type (WT) and IL-17A-deficient (IL-17A(-/-)) mice on the BALB/c background were intraperitoneally (i.p) injected with coxsackievirus B3 (CVB3) for establishing VMC models. Cardiac tissue was obtained on day 7 after CVB3 injection. Myocardial histopathologic changes were observed by hematoxylin-eosin (HE) stained myocardial sections.Expression of IL-27 in heart and serum was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. Furthermore, splenic lymphocytes and peritoneal macrophages were purified 1 week after injection from WT mice.Isolated lymphocytes were cultured in the presence of different concentrations (0 and 25 ng/ml) of recombinant IL-17 (rIL-17) for 24 h. Macrophages were cultured with different concentrations of rIL-17 (0 and 10 ng/ml) for 48 h.IL-27 mRNA expression of cultured cells was assayed by RT-PCR, and their protein level in the culture supernatant was measured by ELISA.

RESULTSCompared with WT mice, significantly less cardiac inflammation was evidenced in the heart of IL-17A-/- mice (0.9 ± 0.3 vs.1.9 ± 0.5) , relative cardiac IL-27 p28 mRNA expressions (1.11 ± 0.24 vs.3.1 ± 0.8) and serum IL-27 protein[(72 ± 18) pg/ml vs.(95 ± 25) pg/ml] were also significantly lower in IL-17A-/- mice (all P < 0.05).In the culture lymphocytes, the relative mRNA (1.02 ± 0.13 vs.1.32 ± 0.21) and protein [(49 ± 9) pg/ml vs.(52 ± 11) pg/ml]expressions of IL-27 p28 and were similar post treatment with 0 and 25 ng/ml rIL-17 (all P > 0.05). Compared with 0 ng/ml rIL-17 culture with macrophages, higher relative mRNA (8.5 ± 3.1 vs.2.2 ± 0.7) and protein [(368 ± 95) pg/ml vs.(150 ± 38) pg/ml] expressions of IL-27 p28 were detected in 10 ng/ml rIL-17 group (all P < 0.05).

CONCLUSIONOur data indicates that cytokine IL-17 may contribute to the secretion of IL-27 in VMC mice.Furthermore, macrophages but not lymphocytes may be the important IL-27-producing immune cells and major target cells for IL-17. Thus,IL-27 and IL-17 might be actively involved in the pathogenesis of VMC.

Animals ; Coxsackievirus Infections ; immunology ; metabolism ; Disease Models, Animal ; Interleukin-17 ; immunology ; Interleukin-27 ; metabolism ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; immunology ; metabolism

BACKGROUND: Fungi, especially Aspergillus flavus, can cause chronic rhinosinusitis with nasal polyposis and modulate host innate immune components. The objective of this study was to examine the serum levels of T helper (Th) cell subset Th1, Th2, and Th17 cytokines and total IgE in patients having chronic rhinosinusitis with nasal polyposis and Aspergillus flavus infection. METHODS: A case-control study including 40 patients with chronic rhinosinusitis with nasal polyposis and 20 healthy controls was conducted. Aspergillus flavus infection was confirmed by standard potassium hydroxide (KOH) testing, culture, and PCR. Serum samples of all patients and controls were analyzed for various cytokines (interleukins [IL]-1β, IL-2, IL-4, IL-6, IL-17, IL-21, IL-27, TGF-β) and total IgE by ELISA. Data from patients with Aspergillus flavus infection and healthy volunteers were compared using the independent t-test and non-parametric Mann-Whitney U test. RESULTS: Aspergillus flavus infection was found in 31 (77.5%) patients with chronic rhinosinusitis with nasal polyposis. IL-1β, IL-17, IL-21, and TGF-β serum levels were significantly higher in these patients than in controls; however, IL-2, IL-4, IL-6, and IL-27 levels were lower. Compared with nine (22.5%) patients without Aspergillus flavus infection, IL-17 level was higher while IL-2 level was lower in patients with Aspergillus flavus infection. Total IgE was significantly higher in patients with Aspergillus flavus infection than in controls. CONCLUSIONS: High levels of IL-17 and its regulatory cytokines in patients with chronic rhinosinusitis with nasal polyposis infected by Aspergillus flavus raise a concern about effective disease management and therapeutic recovery. Surgical removal of the nasal polyp being the chief management option, the choice of post-operative drugs may differ in eosinophilic vs. non-eosinophilic nasal polyposis. The prognosis is likely poor, warranting extended care.
Aspergillus flavus* ; Aspergillus* ; Case-Control Studies ; Cytokines ; Disease Management ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Fungi ; Healthy Volunteers ; Humans ; Immunoglobulin E ; Interleukin-17 ; Interleukin-2 ; Interleukin-27 ; Interleukin-4 ; Interleukin-6 ; Nasal Polyps ; Polymerase Chain Reaction ; Potassium ; Prognosis

BACKGROUNDPrevious studies reported interleukin-27 (IL-27), interferon-γ (IFN-γ), or adenosine deaminase (ADA) alone plays a helpful role in diagnosing tuberculous pleural effusion (TPE). The present study aims at comparing the diagnostic accuracy of pleural IL-27, IFN-γ, and ADA, and investigate the diagnostic accuracy of the combination of IL-27, IFN-γ, or/and ADA for differentiating TPE from pleural effusions with the other etiologies.

METHODSThe concentrations of IL-27, IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion, seven with infectious pleural effusion, and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method. The corresponding biochemical indexs were also simultaneously determined.

RESULTSThe concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant, infectious, and transudative groups. The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions, while much lower than those in infectious effusions. Among these three biomarkers, IL-27 was the most effective for TPE diagnosis, with the cut off value of 900.8 ng/L. IL-27 had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis of TPE from non-TPEs. Combinations of IL-27, IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100%.

CONCLUSIONSCompared to non-TPEs, IL-27, IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods, IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs, especially from MPE. Combinations of the three markers (IL-27, IFN-γ and ADA) yielded the highest sensitivity and specificity. These findings suggest that the applications of a new biomarker, IL-27, alone or with IFN-γ and ADA, may contribute to more efficient diagnosis strategies in the management of tuberculous pleurisy.

Adenosine Deaminase ; blood ; metabolism ; Aged ; Female ; Humans ; Interferon-gamma ; blood ; metabolism ; Interleukin-27 ; blood ; metabolism ; Male ; Middle Aged ; Pleural Effusion ; blood ; metabolism ; Tuberculosis, Pleural ; blood ; diagnosis ; metabolism

OBJECTIVES: To study the significance of interleukin-6 (IL-6) and interleukin-27 (IL-27) in the differential diagnosis of acute respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (NRDS) in preterm infants. METHODS: The preterm infants with the manifestation of respiratory distress who were treated in the Neonatal Diagnosis and Treatment Center, Children's Hospital of Chongqing Medical University, from March to November 2021, were enrolled in this prospective study. According to the diagnosis results, they were divided into two groups: ARDS group (n=18) and NRDS group (n=20). ELISA was used to measure the plasma levels of IL-6 and IL-27. The receiver operating characteristic (ROC) curve was used to analyze the value of each index in the diagnosis of ARDS. RESULTS: The ARDS group had significantly higher plasma levels of IL-6 and IL-27 than the NRDS group (P<0.05). The ROC curve analysis showed that IL-6 had an area under the ROC curve (AUC) of 0.867 for the diagnosis of ARDS, with a sensitivity of 61.1% and a specificity of 95.0% at the cut-off value of 56.21 pg/mL. The ROC curve analysis also showed that IL-27 had an AUC of 0.881 for the diagnosis of ARDS, with a sensitivity of 83.3% and a specificity of 80.0% at the cut-off value of 135.8 pg/mL. CONCLUSIONS Plasma IL-6 and IL-27 can be used as biological indicators for early differential diagnosis of ARDS and NRDS in preterm infants.
Diagnosis, Differential ; Humans ; Infant, Newborn ; Infant, Premature ; Interleukin-27/blood* ; Interleukin-6/blood* ; Pilot Projects ; Prognosis ; Prospective Studies ; ROC Curve ; Respiratory Distress Syndrome/diagnosis* ; Respiratory Distress Syndrome, Newborn/diagnosis*