International immunopharmacology
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Int. Immunopharmacol. · Sep 2018
Cisatracurium induces mast cell activation and pseudo-allergic reactions via MRGPRX2.
Pseudo-allergic reactions occur when patients receive muscle relaxants during perioperative anesthesia. These reactions may result in a serious threat to the patient's life, particularly to a child's life. Cisatracurium, a relatively new NMBA, has resulted in bronchospasms and cardiovascular collapse. However, the mechanisms underlying the anaphylactoid reactions caused by cisatracurium have not been fully elucidated. ⋯ Cisatracurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. Therefore, strategies targeting MRGPRX2 might potentially block cisatracurium-induced pseudo-allergic reactions.
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Int. Immunopharmacol. · Sep 2018
Meta AnalysisEfficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis: A systematic review and meta-analysis of randomized controlled trials.
Numerous biologics are currently licensed for the treatment of psoriasis, including new drugs targeting interleukin-17 (IL-17) and interleukin-23 (IL-23). This meta-analysis evaluated the short-term (12-16 weeks) efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis. Twenty-one randomized clinical trials met the defined inclusion criteria. ⋯ This meta-analysis found that Ixekizumab was the most effective short-term treatment, but was ranked as the most risk therapeutic choice among the biologics involved in this study, while Tildtakizumab was the best alternative in the case of safety. Furthermore, it demonstrated that biologics inhibiting IL-17 were superior to biologics targeting IL-23 in terms of the efficacy, but posed higher risk at the same time. This study might help the clinicians and guideline developers to choose the optimal one among these biologics for the treatment of moderate-to-severe plaque psoriasis.
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Int. Immunopharmacol. · Sep 2018
ReviewImmune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors.
Although T lymphocytes have long been appreciated for their role in the immunosurveillance of cancer, it has been the realization that cancer cells may ultimately escape a response from tumor-reactive T cells that has ignited efforts to enhance the efficacy of anti-tumor immune responses. Recent advances in our understanding of T cell immunobiology have been particularly instrumental in informing therapeutic strategies to overcome mechanisms of tumor immune escape, and immune checkpoint blockade has emerged as one of the most promising therapeutic options for patients in the history of cancer treatment. Designed to interfere with inhibitory pathways that naturally constrain T cell reactivity, immune checkpoint blockade releases inherent limits on the activation and maintenance of T cell effector function. ⋯ S. FDA approval of six checkpoint inhibitors for numerous cancer indications since 2011. In this review, we highlight the clinical success of these FDA-approved immune checkpoint inhibitors and discuss current challenges and future strategies that must be considered going forward to maximize the efficacy of immune checkpoint blockade therapy for cancer.
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Int. Immunopharmacol. · Aug 2018
Bone marrow derived M2 macrophages protected against lipopolysaccharide-induced acute lung injury through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses.
Acute lung injury (ALI) is characterized by aggravated inflammatory responses and the subsequent alveolar-capillary injury for which there are no specific therapies available currently. The present study was designed to investigate the protective roles of bone marrow derived M2 macrophages (M2 BMDMs) in lipopolysaccharide (LPS) induced ALI. M2 BMDMs were obtained from bone marrow cells stimulated with M-CSF and IL-4. ⋯ Further, M2 BMDMs suppressed the TNF-α, IL-1β and IL-6 production, while increased the IL-10 production. Blockade of PD-L1/PD-1 pathway reversed cytokines production of M2 BMDMs in the BALF. These findings indicated that M2 BMDMs might be a promising therapeutic strategy for LPS-induced ALI through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses.
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Int. Immunopharmacol. · Aug 2018
Inhibition of acetaminophen-induced hepatotoxicity in mice by exogenous thymosinβ4 treatment.
To study the effects of exogenous thymosinβ4 (Tβ4) treatment in acetaminophen (APAP)-induced hepatotoxicity. ⋯ Exogenous Tβ4 treatment exerts protective effects against APAP-induced hepatotoxicity in mice. The underneath molecular mechanisms may involve autophagy enhancement and inhibition of oxidative stress by Tβ4.