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ID PMID Title PublicationDate abstract
29576918 Nonspanning Total Wrist Arthrodesis with a Low-Profile Locking Plate. 2018 Apr Purpose  This study aims to compare the outcomes and complications of our technique for nonspanning total wrist arthrodesis using a locking plate with the standard carpometacarpal spanning technique. Methods  A retrospective review of charts was performed to identify patients who underwent total wrist arthrodesis by the senior author (S.W.W.). We compared the outcomes of 15 cases of nonspanning wrist fusion with a 2.4/2.7 mm locking T plate to 11 cases of spanning wrist fusion with a 2.7/3.5 mm locking compression plate. Minimum follow-up was 3 months. Indications for fusion included rheumatoid arthritis, posttraumatic arthritis, Kienböck's disease, primary osteoarthritis, juvenile inflammatory arthropathy, psoriasis, brachial plexopathy, failed hemi or total wrist arthroplasty, failed four-corner fusion, and failed proximal row carpectomy. The primary outcome was fusion. Secondary outcomes included time to union, patient-rated wrist evaluation score, numerical rating scale pain score, grip strength, and complications. Results  All the wrists got fused. There were no significant differences in objective and subjective outcomes between cohorts. There were three complications (27%) in the spanning group, including tendon rupture and peri-implant fracture at the third metacarpal. This was compared with three complications (20%) in the nonspanning group, consisting of hardware removal. Discussion  We achieved similar fusion rates employing both spanning and nonspanning total wrist arthrodesis techniques, without necessitating carpometacarpal arthrodesis in the latter. Complications associated with our method were comparably less severe than those reported in the literature. We advocate nonspanning arthrodesis as an alternative method for total wrist fusion with a high union rate and minimal risk of complications at the carpometacarpal joint. Level of Evidence  Therapeutic level IV.
30314337 Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren's Syndrome with 2018 Oct 11 The risk of developing lymphoma in patients with Sjögren's syndrome (SS) is 44 times higher than in the normal population with the most common lymphomas derived from marginal zone B (MZB) cells. Current understanding of the role of MZB cells in SS is primarily based on salivary gland pathology, while their contextual association with lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a SS mouse model (thrombospondin-1 deficient (TSP1(-/-))) with well-characterized ocular disease. We determined the frequency, localization, and cytokine profiles of MZB cells and their association with an antibody response in TSP1(-/-) mice treated with a TSP-derived peptide. A significantly increased frequency of MZB cells was detected in the spleens and lacrimal glands of TSP1(-/-) mice in comparison to wild-type tissues as detected by immunostaining. An altered cytokine profile of TSP1(-/-) MZB cells was supportive of T helper 17 (Th17)-related pathogenesis. A significantly reduced antibody response and the splenic MZB compartment against an eye-derived antigen were noted in TSP-derived peptide-treated mice. These changes correspond with the previously reported ability of the peptide to ameliorate SS-related ocular manifestations. Collectively, our results demonstrate dysregulation of MZB cells in TSP1(-/-) mice and highlight their role in the context of SS-related chronic ocular surface disease.
30156548 The evaluation of disease activity in Sjögren's syndrome based on the degree of MALT invo 2018 May OBJECTIVES: To investigate if indicators of a heavier involvement of mucosa-associated lymphoid tissue (MALT) in primary Sjögren's syndrome (pSS), i.e. persistent salivary gland (SG) swelling and cryoglobulinaemia, might better evaluate the lymphoma risk compared to the ESSDAI. Therefore, the current concept of disease activity of pSS should be re-evaluated, based solely on ESSDAI. METHODS: A cohort of 255 pSS patients, including 30 pSS with B-cell lymphoma, was investigated. Three subgroups were distinguished, i.e. pSS developing lymphoma in the follow-up (n=12), pSS with lymphoma at cohort inclusion (n=18), and control pSS not developing lymphoma in the follow-up (n=225). SG swelling, cryoglobulinaemia and ESSDAI were evaluated at baseline, in the follow-up to one year before lymphoma diagnosis, and at lymphoma diagnosis. RESULTS: SG swelling and/or cryoglobulinaemia at baseline were significantly higher (p=0.0003) in pSS patients evolving into lymphoma if compared to pSS controls, while ESSDAI showed no significant difference. Both SG swelling and cryoglobulinaemia persisted and sometimes developed ex novo in the follow-up. SG swelling and cryoglobulinaemia were present in 24/30 (80%) cases the time of lymphoma diagnosis, and lymphoma itself was usually of MALT/marginal zone histotype (90%), leading to peculiar manifestation of lymphoma in pSS. CONCLUSIONS: The autoimmune and lymphoproliferative involvement of MALT is the biological substrate of pSS. If this involvement is heavier, as reflected by SG swelling and cryoglobulinaemia, disease activity may be considered higher, and the risk of lymphoma is increased. The current concept and evaluation of activity of pSS, based solely on the ESSDAI, needs revision.
29465536 Primary cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhos 2018 Feb RATIONALE: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. PATIENT CONCERNS: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department. DIAGNOSES: Due to the patient's symptoms, laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS. INTERVENTIONS: She was subsequently treated with a combination of ursodeoxycholic acid (UDCA), prednisone, and azathioprine. OUTCOMES: While this treatment can achieve therapeutic success, it cannot prevent complications from cirrhosis. This patient remains alive but experienced an emergent gastrointestinal hemorrhage. LESSONS: While we acknowledge that this is a single case, these findings extend our knowledge of immunological diseases associated with PCA and suggest a common, immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS. After 12 years of follow up, clinical manifestations have developed, and these autoimmune diseases have progressed. The combination of UDCA, prednisone, and azathioprine can achieve therapeutic success but cannot prevent disease progression. Routine follow up for this patient is necessary to document disease progression.
30067782 Dysregulation of NF-kB in glandular epithelial cells results in Sjögren's-like features. 2018 The autoimmune disease primary Sjögren's syndrome (pSS) is characterized by hypofunction of the salivary glands (SGs), the cause of which is not correlated to lymphocytic SG infiltration, as prevailing dogma often states. We knocked out the NF-κB proinflammatory pathway inhibitor A20 in keratin14+ epithelial cells, to investigate if immune activated epithelial cells are capable of initiating pSS SG hallmarks. We show that immune activated epithelial cells can cause T cell dominated leukocytic infiltration and immune foci development of the SGs, reflecting the early clinical picture. Infiltrating leukocytes invaded striated ducts, similar to early stage lymphoepithelial lesions observed clinically. Expression of proinflammatory cyto-/chemokines IFNɣ, TNFα, IL-6, CXCL10 and CXCL13 increased in A20-/- SGs, and functionally both volume and mucin 10 content of whole stimulated saliva from A20-/- mice was significantly reduced. Epithelial cells may therefore represent the initial trigger for pSS SG pathologies, as opposed to simple reactionaries to pre-existing stimuli.
29679709 Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients usin 2018 Jul Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRβ variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8-2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTD*E) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.
28834412 Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving D 2018 May OBJECTIVE: To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease-modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis. METHODS: We conducted a systematic review and meta-analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non-TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle-Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model. RESULTS: Twenty-five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8-2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5-2.6]), non-TNF biologics (6.1% [95% CI 0.0-16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2-4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1-15.5]) than in those who did not (14.6% [95% CI 4.3-29.0]). CONCLUSION: We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.
30513621 Reduced Corneal Innervation in the CD25 Null Model of Sjögren Syndrome. 2018 Nov 30 Decreased corneal innervation is frequent in patients with Sjögren Syndrome (SS). To investigate the density and morphology of the intraepithelial corneal nerves (ICNs), corneal sensitivity, epithelial cell proliferation, and changes in mRNA expression of genes that are involved in autophagy and axon targeting and extension were assessed using the IL-2 receptor alpha chain (CD25 null) model of SS. ICN density and thickness in male and female wt and CD25 null corneas were assessed at 4, 6, 8, and 10/11 wk of age. Cell proliferation was assessed using ki67. Mechanical corneal sensitivity was measured. Quantitative PCR was performed to quantify expression of beclin 1, LC3, Lamp-1, Lamp-2, CXCL-1, BDNF, NTN1, DCC, Unc5b1, Efna4, Efna5, Rgma, and p21 in corneal epithelial mRNA. A significant reduction in corneal axon density and mechanical sensitivity were observed, which negatively correlate with epithelial cell proliferation. CD25 null mice have increased expression of genes regulating autophagy (beclin-1, LC3, LAMP-1, LAMP-2, CXCL1, and BDNF) and no change was observed in genes that were related to axonal targeting and extension. Decreased anatomic corneal innervation in the CD25 null SS model is accompanied by reduced corneal sensitivity, increased corneal epithelial cell proliferation, and increased expression of genes regulating phagocytosis and autophagy.
30007092 Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation 2018 Oct BACKGROUND: The human salivary gland (HSG) cell line has so far been used as in vitro models for study of the influence of cytokines and pharmacologic agents on salivary glands, as well as a model system for inflammation in Sjögren's syndrome (SS). This study aimed to determine the effect of IL-17 on IL-6 production and the underlying molecular mechanism regulated by the HSG cell line. METHODS: Immunofluorescence analyses, RT-PCR, and Western blot were conducted to evaluate the IL-17 receptor (IL-17R) expression in cultured HSG cells. Real-time PCR and ELISA were then utilized to establish the mRNA and protein levels of IL-6 in IL-17-stimulated HSG cells. Western blot, flow cytometry, immunofluorescence, and inhibitor analyses were conducted to elucidate the involved signaling pathways. RESULTS: The HSG cells reliably expressed the IL-17R mRNA and its encoded surface-bound protein. The expression of IL-6 mRNA and protein was upregulated by stimulation of HSG cells with IL-17; this effect was impeded by IL-17- or IL-17R-neutralizing antibodies. IL-17 stimulation ended up with the fast phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), Akt, and translocation of nuclear factor-kappaB (NF-κB) in the HSG cells. p38 MAPK, Akt, and NF-κB inhibitors significantly subdued IL-6 generation in HSG cells stimulated by IL-17. PD98059, an ERK inhibitor, decreased IL-6 generation under low dose of IL-17 but not with high dose. CONCLUSIONS: The HSG cells expressed IL-17R and reacted to IL-17 to generate IL-6 via the stimulation of ERK, p38 MAPK, Akt, and NF-κB signaling pathways.
29634071 [

One steroid injection in combination with HIV-medication resulted in a total adrenal i

 2018 Apr 5 This case report describes a woman living with HIV on treatment including ritonavir-boosted darunavir, who suffered complete secondary adrenal insufficiency after a single intra-articular injection of the corticosteroid triamcinolone. There is a known pharmacological interaction between ritonavir and those corticosteroids which are metabolised by the CYP3A4 pathway. This interaction may lead to complete adrenal insufficiency, which is a life-threatening condition. Adrenal insufficiency must be promptly diagnosed and hydrocortisone replacement started. People living with HIV should be on lifelong antiretroviral treatment, and corticosteroids are common in the treatment of many different conditions seen by various specialists. This case highlights that not only physicians engaged in HIV treatment need to be aware of this important interaction.
29631064 Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibit 2018 Jun The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically the morbidity and mortality rates for these patients. Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome. The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation. In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.
29551295 Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndr 2018 Jul Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls. We found that SS patients at high risk for lymphoma and those with established lymphoma display high serum cf-DNA levels, substantial extranuclear DNA accumulations in PBMC and SG tissues, a unique NLRP3 inflammasome gene signature in PBMC, and significantly increased serum IL-18 and ASC levels. In these patients, the circulating monocytes manifested NLRP3 inflammasome activation and increased response to NLRP3 stimuli, whereas SG-infiltrating macrophages exhibited signs of NLRP3 activation and pyroptosis. Cell-free nucleic acids isolated from patients' sera competently primed the activation of both NLRP3 and AIM2 inflammasomes in healthy monocytes. SS patients also manifested diminished DNaseI activity in serum and DNaseII expression in PBMC, which inversely correlated with indices of inflammasome activation. DNaseII gene-silencing in healthy monocytes led to cytoplasmic DNA deposition and activation of inflammasome-related genes and of caspase1. Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.
29648683 Long-Term Outcomes Following Achievement of Clinically Inactive Disease in Juvenile Idiopa 2018 Sep OBJECTIVE: Potential targets for treat-to-target strategies in juvenile idiopathic arthritis are minimal disease activity (MDA) and clinically inactive disease (CID). We undertook this study to compare short- and long-term outcomes following achievement of MDA and CID on the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et al's preliminary criteria. METHODS: Children recruited to the Childhood Arthritis Prospective Study, a UK multicenter inception cohort, were selected if they were recruited prior to January 2011 and diagnosed as having oligoarthritis or rheumatoid factor-negative or -positive polyarthritis. One year following diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both Wallace et al's preliminary criteria and the cJADAS10. Associations were tested between those disease states and functional ability, absence of joints with limited range of motion, psychosocial health, and pain at 1 year and annually to 5 years. RESULTS: Of 832 children, 70% were female and the majority had oligoarthritis (68%). At 1 year, 21% had achieved CID according to both definitions, 7% according to Wallace et al's preliminary criteria alone, and 16% according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children in the entire cohort achieved MDA without also achieving CID. Achieving either early CID state was associated with a greater absence of joints with limited range of motion. However, only CID according to the cJADAS10 was associated with improved functional ability and psychosocial health. Achieving CID was superior to achieving MDA in terms of short- and long-term pain and the absence of joints with limited range of motion. CONCLUSION: CID on the cJADAS10 may be preferable as a treatment target to CID on Wallace et al's preliminary criteria in terms of both feasibility of application and long-term outcomes.
29504848 Signalling pathways identified in salivary glands from primary Sjögren's syndrome patient 2018 May A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions. A microarray analysis was performed on SG from 6 pSS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development, inflammatory responses, and lymphoma development were assessed. Real-time PCR was carried out on SG from 14 pSS patients and 15 non-SS controls to account for IL6, IL10, and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted. Our results indicate signalling pathways identified in SG of pSS patients displayed genes leading to prominent adipose tissue development and reduced mitochondrial fatty acid beta-oxidation (ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL), inflammatory responses (IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14, and CD48), and lymphoma development via JAK-STAT signalling (STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1, and BAK1). Genes involved in interferon production and signalling were also detected (IRF1, IRF9, and IRF7), in addition to IL6, IL10, and IL17. Higher mRNA levels of IL6, IL17 and IL10 were observed in the SG of pSS patients compared to controls. Moreover, IL17 positive cells were detected mostly interstitially in the SG and around adipocytes, also within the focal infiltrates. In conclusion, adipocyte development seems to be more prominent in the SG of pSS patients, where adipose tissue replacement is also evident. Whether this is due to disease progression, or the repair process, remains to be investigated. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.
30635081 Inflammatory response and its relation to sphingolipid metabolism proteins: Chaperones as 2019 Lysosome is the organelle responsible for breaking down macromolecules to maintain homeostasis and to fight infection. The disruption of normal lysosomal function due to mutations in the sphingolipid metabolism proteins leads to a class of lysosomal storage diseases (LSDs). Defective autophagy and activation of inflammation are observed in most LSDs. The crosstalk between these key metabolic pathways suggests that therapeutic approaches used in the treatment of LSDs may provide anti-inflammatory therapies against chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease. Here, we review the role of sphingolipids in the inflammatory response and build a protein-protein interaction network for proteins related with sphingolipid metabolism and inflammation to identify key interaction partners for the crosstalk between sphingolipids and inflammation. In addition, we present an overview of LSDs in relation with sphingolipids and inflammation, and review the pharmacological chaperones identified for these diseases.
30464573 Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. 2018 The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, and Rel-B proteins, which form homo- or heterodimers and remain as an inactive complex with the inhibitory molecules called IκB proteins in resting cells. Two distinct NF-κB signaling pathways have been described: 1) the canonical pathway primarily activated by pathogens and inflammatory mediators, and 2) the noncanonical pathway mostly activated by developmental cues. The most abundant form of NF-κB activated by pathologic stimuli via the canonical pathway is the p65:p50 heterodimer. Disproportionate increase in activated p65 and subsequent transactivation of effector molecules is integral to the pathogenesis of many chronic diseases such as the rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even neurodegenerative pathologies. Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB p65 in the context of chronic inflammation.
30433838 JAK-inhibitors in dermatology: current evidence and future applications. 2019 Nov The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a ubiquitous intracellular signaling network. Selective JAK-inhibitors have anti-inflammatory properties and have been approved in many countries for the treatment of rheumatoid arthritis (tofacitinib, baricitinib) and myelofibrosis or polycythemia vera (ruxolitinib). The aim of the publication was to summarize and critically analyze the efficacy and safety of JAK-inhibitors in skin diseases, such as psoriasis, alopecia areata, atopic dermatitis and vitiligo. Databases PubMed, Scopus and EBSCO were searched. After exclusions, 17 articles were analyzed (11 randomized clinical trials, 4 case reports, 1 retrospective study of a case series and 1 nonrandomized pilot study). The strongest evidence of JAK-inhibitor efficacy was established for treatment of psoriasis. Additionally, data are available on the potential efficacy of JAK-inhibitors in alopecia areata, atopic dermatitis and vitiligo. Mostly, JAK-inhibitors are used orally. However, there are studies showing efficacy of topical administration of this group of drugs in psoriasis and vitiligo. Further research is needed, especially the head-to-head comparison studies with JAK-inhibitors and current therapeutic methods to verify the superiority of this new group of drugs in dermatological diseases.
30268393 To bee or not to bee: The potential efficacy and safety of bee venom acupuncture in humans 2018 Nov Bee venom acupuncture is a form of acupuncture in which bee venom is applied to the tips of acupuncture needles, stingers are extracted from bees, or bees are held with an instrument exposing the stinger, and applied to acupoints on the skin. Bee venom is a complex substance consisting of multiple anti-inflammatory compounds such as melittin, adolapin, apamin. Other substances such as phospholipase A2 can be anti-inflammatory in low concentrations and pro-inflammatory in others. However, bee venom also contains proinflammatory substances, melittin, mast cell degranulation peptide 401, and histamine. Nevertheless, in small studies, bee venom acupuncture has been used in man to successfully treat a number of musculoskeletal diseases such as lumbar disc disease, osteoarthritis of the knee, rheumatoid arthritis, adhesive capsulitis, and lateral epicondylitis. Bee venom acupuncture can also alleviate neurological conditions, including peripheral neuropathies, stroke and Parkinson's Disease. The treatment has even been piloted in one series to alleviate depression. An important concern is the safety of bee venom. Bee venom can cause anaphylaxis, and several deaths have been reported in patients who successfully received the therapy prior to the adverse event. While the incidence of adverse events is unknown, the number of published reports of toxicity is small. Refining bee venom to remove harmful substances may potentially limit its toxicity. New uses for bee venom acupuncture may also be considered.
30246692 Role of Interleukin-37 in Inflammatory and Autoimmune Diseases. 2018 Sep Interleukin-1 family 7 (IL-1F7) is a novel member of IL-1F cytokines. IL-1F7 is more commonly known as IL-37. IL-37 can join the α-subunit of the IL-18 receptor, or IL-18 binding protein (IL-18BP), and binding of these proteins can enhance the IL-18 suppression. IL-37 also translocates to the cell nucleus and affects gene transcription. IL-37 inhibits the phosphorylation of p38 mitogen-activated protein kinases. Almost all reports showed that IL-37 has remarkable anti-inflammatory activity. IL-37 plays an important role in a variety of inflammatory and autoimmune diseases, as well. Recently, studies demonstrated that the expression of IL-37 is abnormal in many diseases such as inflammatory bowel diseases, inflammatory respiratory diseases, atherosclerosis, hepatitis, obesity, contact hypersensitivity, Graves' disease, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Behcet's disease. Here, we will review the biological characteristics of IL-37 and its key roles in various inflammatory and autoimmune diseases.
30083153 The Role of Efferocytosis in Autoimmune Diseases. 2018 Apoptosis happens continuously for millions of cells along with the active removal of apoptotic debris in order to maintain tissue homeostasis. In this respect, efferocytosis, i.e., the process of dead cell clearance, is orchestrated through cell exposure of a set of "find me," "eat me," and "tolerate me" signals facilitating the engulfment of dying cells through phagocytosis by macrophages and dendritic cells. The clearance of dead cells via phagocytes is of utmost importance to maintain the immune system tolerance to self-antigens. Accordingly, this biological activity prevents the release of autoantigens by dead cells, thus potentially suppressing the undesirable autoreactivity of immune cells and the appearance of inflammatory autoimmune disorders as systemic lupus erythematous and rheumatoid arthritis. In the present study, the apoptosis pathways and their immune regulation were reviewed. Moreover, efferocytosis process and its impairment in association with some autoimmune diseases were discussed.