• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.569-577
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• 2017

Sepsis is a syndrome characterized by systemic inflammatory responses to a severe infection. Acute hyper-inflammatory reactions in the acute phase of sepsis have been considered as a primary reason for organ dysfunction and mortality, and advances in emergency intervention and improved intensive care management have reduced mortalities in the early phase. However it has been recognized that increased deaths in the late phase still maintain sepsis mortality high worldwide. Patients recovered from early severe illness are unable to control immune system with sepsis-induced immunosuppression such as immunological tolerance, exhaustion and apoptosis, which make them vulnerable to nosocomial and opportunistic infections ultimately leading to threat to life. Based on strategies to reverse immunosuppression, recent developments in sepsis therapy are focused on molecules having immune enhancing activities. These efforts are focused on defining and revising the immunocompromised status associated with long-term mortality.

• Childhood Kidney Diseases
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• v.26 no.1
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• pp.11-17
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• 2022

BK polyomavirus (BKPyV) is a ubiquitous virus residing in the kidney tubules and is clinically significant only in immunocompromised patients. In clinical practice, BKPyV is a causative pathogen of BKPyV-associated nephropathy (BKVAN) in kidney allograft recipients or hemorrhagic cystitis of hematopoietic stem cell transplant recipients. Currently, there is no effective treatment for BKVAN; therefore, careful monitoring and prudent modification of immunosuppression are necessary to prevent BKVAN. In this article, the epidemiology, pathophysiology, and current management strategies for BKVAN are reviewed.

• Clinical and Experimental Pediatrics
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• v.58 no.10
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• pp.402-405
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• 2015

IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage.

• Archives of Craniofacial Surgery
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• v.13 no.2
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• pp.85-94
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• 2012

The world's first face transplantation was performed in France, in 2005. Since then, 21 cases of face transplantation have been performed. Face transplantation is one of the most prominent part of composite tissue allotransplantation (CTA) along with hand transplantation. Since these fields are not deal with life-saving organs, there are many arguments about immunosuppression therapy. Recent paradigm of face transplantation shows that surgical ranges are expanded from partial face transplantation to full face transplantation. Most immunosuppression protocols are triple therapy, which consists of tacrolimus (FK-506), mycophenolate mofetil and prednisolone. Anatomical researches, immunosuppression, and immunotolerance take great parts in the researches of CTA. The medical fields directly related to face transplantation are microsurgery, immunology, and transplantation. Nowadays, each field is performed widely. Therefore people, even medical teams think face transplantation could be easily realized, sooner or later. But there are lots of things that should be prepared for not only practice and immunosuppression therapy but also for the cooperation with relevant fields. That's the reason why only 21 cases of face transplantation have been done, while more than 70 cases of hand transplantation have been done in the past years. Especially in Korea, brain death patients are not enough even for organ transplantation and furthermore there are some troubles in taking part in the society of transplantation. Face transplantation has lots of problems concerning variable medical fields, administration, society, ethics, and laws. Therefore, for the realization of face transplantation in Korea, not only medical skills but also political powers are needed.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.124-129
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• 1999

The present study was undertaken to investigate the effect of biphenyl dimethyl idcarboxylate (PMC) on the humoral immunosuppression by ketoconazole (KCZ) in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Mice were immunized an challenged with challenged red blood cells (SRBC). The results of the present study are summarized as follows; a gain of body weight and relative weights of spleen and liver were significantly increased by combination of PMC and KCZ, as compared with those in mice treated with KCZ alone. Splenic plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were greatly enhanced by the combination of PMC and KCZ, compared with treatment of KCZ alone. The elevation of serum glutamicpyruvic transminase (S-GPT) and total protein levels caused by KCZ were reduced to normal level by the combination of PMC and KCZ. In addition, lower serum albumin and A/G ratio were also increased to normal level. These findings indicate that PMC has a protective effect against KCZ-induced humoral immunosuppression.

• Molecules and Cells
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• v.22 no.1
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• pp.1-7
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• 2006

The NFAT family of transcription factors plays pivotal roles in the development and function of the immune system. Their activation process is tightly regulated by calcium-dependent phosphatase calcineurin and has been a target of the immunosuppressive drugs cyclosporin A and FK-506. Although the clinical use of these drugs has dramatically increased the success of organ transplantation, their therapeutic use is limited by severe side effects. Recent studies for the calcineurin/NFAT signaling pathway have identified a number of cellular proteins that inhibit calcineurin function. Specific peptide sequences that interfere with the interaction between calcineurin and NFAT have also been characterized. Moreover, diverse approaches to identify small organic molecules that modulate NFAT function have been performed. This review focuses on the recent advances in our understanding of the inhibitory modulation of NFAT function, which may open up the additional avenues for immunosuppressive therapy.

• Clinical and Experimental Pediatrics
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• v.49 no.8
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• pp.821-829
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• 2006

Hemophilia is the most common coagulation disorder. It has a long history. Hemophilia A is caused by FVIII gene mutation, and hemophilia B by FIX gene mutation. Those genes are located on X chromosome long arm. Bleedings in hemophiliacs predominantly occur in joints and muscles. Because those site are insufficient in tissue factor to induce hemostasis. Among joints knee, ankle and elbow are most frequently affected because their synovial structure is vulnerable to injury compared to other joints. Hemophilia is diagnosed with factor assay. Severe hemophilia is below 1% of FVIII : C, moderate between 1% and 5%, mild over 5%. Carrier detection and prenatal diagnosis have been conducted with RFLP-based linkage analysis and DNA sequencing. Mainstay of treatment is factor replacement therapy so far. Bleedings can be controlled by infusion of factor concentrates. Hemophilc arthropathy and muscle contracture are representative sequelae. Complications of facotor replacement therapy are inhibitor development and infections. Hemophiliacs with inhibitor should be managed with large dose factor concentrate, bypassing agent, ITI and immunosuppression. Ultimately, hemophilia could be cured by gene therapy.

• BMB Reports
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• v.56 no.5
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• pp.314-319
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• 2023

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-β effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-β, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-β plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-β upregulated SIRT1 protein expression in endothelial cells in a protein synthesis-independent manner. IFN-β plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-β plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-β plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.1-6
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• 2004

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.117-123
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• 2005

The immune response to any stimulus is complex, requiring coordinated action by several types of cells in a tightly regulated sequence. Thus, a physical stress such as exercise may act at any number of points in the complex sequence of events collectively termed the immune response. Although exercise causes many propound changes in parameters of immune function, the nature and magnitude of such changes rely on several factors including the immune parameters of interest; type, intensity, and duration of exercise; fitness level or exercise history of the subject; environmental factors such as ambient temperature and humidity. Although regular moderate exercise appears to be important factor for increasing immunity, Athletes are susceptible to illness, in particular upper respiratory track infection, during periods of intense training and after competition. In addition, in elite athletes, frequent illness is associated with overtraining syndrome, a neuroendocrine disorder resulting from excessive training. Through this paper, we want to investigate the effects of exercise on the immunosuppression such as exercise induced lymphopenia, asthma, anaphylaxis, URT (upper respiratory track), and TB (tuberculosis) infection. and also, we want to suggest a direct mechanism, protection and therapy of exercise induced immunosuppression.