A complex pathophysiological mechanism is involved in brain injury following cerebral infarction. The neurovascular unit (NVU) is a complex multi-cellular structure consisting of neurons, endothelial cells, pericyte, astrocyte, microglia and extracellular matrix, etc. The dyshomeostasis of NVU directly participates in the regulation of inflammatory immune process. The components of NVU promote inflammatory overreaction and synergize with the overactivation of autonomic nervous system to initiate stroke-induced immunodepression (SIID). SIID can alleviate the damage caused by inflammation, however, it also makes stroke patients more susceptible to infection, leading to systemic damage. This article reviews the mechanism of SIID and the roles of NVU in SIID, to provide a perspective for reperfusion, prognosis and immunomodulatory therapy of cerebral infarction.
Humans ; Endothelial Cells ; Stroke ; Neurons/physiology* ; Immunosuppression Therapy/adverse effects* ; Cerebral Infarction

BACKGROUND: Optimal tacrolimus (TAC) trough levels for different periods after kidney transplantation (KT) has not been definitely established. This study aimed to investigate transplant outcomes of low-level (LL) and standard-level (SL) TAC according to post-transplant period. METHODS: A total of 278 consecutive kidney transplant recipients (KTRs) receiving TAC-based immunosuppression were divided into LL and SL-TAC groups (4–7 and 7–12 ng/mL for 0–2 months, 3–6 and 6–10 ng/mL for 3–6 months, 2–5 and 5–8 ng/mL for 7–12 months, respectively) according to TAC trough level at each period. We compared estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA), calcineurin inhibitor (CNI) toxicity, opportunistic infection, and allograft survival. RESULTS: SL-TAC group showed significantly higher mean eGFR at 0–2 months than LL-TAC group (72.1 ± 20.3 vs. 64.2 ± 22.7 mL/min/1.73m2; P = 0.003). Incidence of BPAR at 7–12 months was significantly lower in SL-TAC group than in LL-TAC group (0.0% vs. 3.9%; P = 0.039). Patients with persistent SL-TAC lasting 12 months showed higher eGFR at 7–12 months than those with persistent LL-TAC (65.5 ± 13.0 vs. 57.9 ± 13.9 mL/min/1.73m2; P = 0.007). No significant differences in dnDSA, CNI toxicity, serious infections, or allograft survival were observed. CONCLUSIONS: Maintenance of proper TAC trough level after 6 months could reduce BPAR without adverse drug toxicities in KTRs. Moreover, persistent SL-TAC during the first year after KT might have a beneficial effect on a trend for a lower incidence of dnDSA and better renal allograft function.
Allografts ; Calcineurin ; Drug-Related Side Effects and Adverse Reactions ; Glomerular Filtration Rate ; Humans ; Immunosuppression ; Incidence ; Kidney Transplantation ; Kidney ; Opportunistic Infections ; Tacrolimus ; Transplant Recipients

OBJECTIVEThe purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved.

METHODSICR mice and mouse lymphoma cell line (EL-4 cells) was used. The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1, IL-10, PKA and cAMP were estimated with ELISA.

RESULTSAt 12 h after irradiation, the expression of Nrp1 increased significantly in 4.0 Gy group, compared with sham-irradiation group (P<0.05) in the spleen and thymus, respectively, when ICR mice received whole-body irradiation (WBI). Meanwhile the synthesis of Interleukin 10 (IL-10) and transforming growth factor-β1 (TGF-β1) increased significantly after high dose irradiation (HDR) (> or = 1.0 Gy). In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation.

CONCLUSIONThese results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.

Animals ; Calcineurin ; genetics ; metabolism ; Cyclic AMP ; metabolism ; Dose-Response Relationship, Radiation ; Female ; Gene Expression Regulation ; radiation effects ; Immunosuppression ; Interleukin-10 ; genetics ; metabolism ; Lymphocyte Subsets ; physiology ; Male ; Mice ; Neuropilin-1 ; genetics ; metabolism ; Phosphoinositide Phospholipase C ; genetics ; metabolism ; Protein Kinases ; genetics ; metabolism ; Signal Transduction ; Transforming Growth Factor beta ; genetics ; metabolism ; Whole-Body Irradiation ; adverse effects

INTRODUCTIONDue to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure.

METHODSFrom January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit.

RESULTSAverage time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis.

CONCLUSIONIn RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.

Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Bacterial Infections ; complications ; Comorbidity ; Creatinine ; blood ; Female ; Graft Rejection ; Hospital Mortality ; Humans ; Immunosuppression ; adverse effects ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Intensive Care Units ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pneumonia ; complications ; microbiology ; Renal Insufficiency ; complications ; immunology ; surgery ; Respiratory Insufficiency ; complications ; Retrospective Studies ; Risk Factors

No abstract available.
Animals ; Antigen-Presenting Cells/immunology ; Graft Rejection/immunology/*prevention & control ; Graft Survival ; *Histocompatibility ; Humans ; Immunosuppression/*methods ; Intercellular Adhesion Molecule-1/immunology ; Isoantigens/*immunology ; Organ Transplantation/*adverse effects ; *Transplantation Tolerance

A 51-yr-old female was referred to our outpatient clinic for the evaluation of generalized edema. She had been diagnosed with idiopathic thrombocytopenic purpura (ITP). She had taken no medicine. Except for the ITP, she had no history of systemic disease. She was diagnosed with systemic lupus erythematosus. Immunosuppressions consisting of high-dose steroid were started. When preparing the patient for discharge, a generalized myoclonic seizure occurred at the 47th day of admission. At that time, the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome. Brain MRI and EEG showed brain atrophy without other lesion. The seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit. The patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone, insulin glargine and nateglinide. The patient remained asymptomatic under maintenance therapy with deflazacort and without insulin or medication for blood sugar control.
Edema ; Epilepsies, Myoclonic/complications/drug therapy ; Female ; Humans ; Hyperglycemia/*chemically induced ; Immunosuppression ; Insulin/therapeutic use ; Lupus Nephritis/*complications/drug therapy ; Middle Aged ; Prednisolone/administration & dosage/*adverse effects/therapeutic use ; Purpura, Thrombocytopenic, Idiopathic/complications/*drug therapy

Infection of the central nervous system with Nocardia sp. usually manifests as supratentorial abscesses. Supratentorial and cerebellar abscesses from infection with Nocardia sp. following immunosuppression with long-term corticosteroids for idiopathic thrombocytopenia (ITP) have not been reported. An 83 years-old, human immunodeficiency virus (HIV)-negative, polymorbid male with ITP for which he required corticosteroids since age 53 years developed tiredness, dyspnoea, hemoptysis, abdominal pain, and progressive gait disturbance. Imaging studies of the lung revealed an enhancing tumour in the right upper lobe with central and peripheral necrosis, multiple irregularly contoured hyperdensities over both lungs, and right-sided pleural effusions. Sputum culture grew Nocardia sp. Neurological diagnostic work-up revealed dysarthria, dysphagia, ptosis, hypoacusis, tremor, dysdiadochokinesia, proximal weakness of the lower limbs, diffuse wasting, and stocking-type sensory disturbances. The neurological deficits were attributed to an abscess in the upper cerebellar vermis, myopathy from corticosteroids, and polyneuropathy. Meropenem for 37 days and trimethoprime-sulfamethoxazole for 3 months resulted in a reduction of the pulmonary, but not the cerebral lesions. Therefore, sultamicillin was begun, but without success. Long-term therapy with corticosteroids for ITP may induce not only steroid myopathy but also immune-incompetence with the development of pulmonary and cerebral nocardiosis. Cerebral nocardiosis may not sufficiently respond to long-term antibiotic therapy why switching to alternative antibiotics or surgery may be necessary.
Adrenal Cortex Hormones/*adverse effects/*therapeutic use ; Aged, 80 and over ; Cerebellar Diseases/*chemically induced/*diagnosis/pathology ; Humans ; Immunosuppression ; Male ; Muscular Diseases/*chemically induced/pathology ; Nocardia Infections/*diagnosis ; Purpura, Thrombocytopenic, Idiopathic/*drug therapy

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study. On postoperative day 6, continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein. Based on histological findings, acute rejection was the suspected cause. The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies. The patient was discharged on the 30th postoperative day. It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection, and can be successfully treated by anti-rejection therapy.
Adult ; Antilymphocyte Serum ; therapeutic use ; Graft Rejection ; prevention & control ; Hepatic Artery ; diagnostic imaging ; physiology ; Hepatolenticular Degeneration ; surgery ; Humans ; Immunosuppression ; methods ; Immunosuppressive Agents ; therapeutic use ; Liver Transplantation ; adverse effects ; methods ; Living Donors ; Male ; Portal Vein ; diagnostic imaging ; physiopathology ; Tacrolimus ; therapeutic use ; Ultrasonography

As allogeneic blood transfusion plays a role in clinical treatment effects, it also produces a number of immune-related side effects, such as the increased rate of postoperative infection, the rising relapse rate of malignant resection and so on. All those factors, such as CD200 surface molecule of allogeneic mononuclear cells, interleukin, sHLA and sFasL which are detached from the leukocyte surface during the period of storage, and serum bioactive molecules related to a certain degree with the occurrence of transfusion-related immunomodulation (TRIM). The clinical controlled trials, laboratory researches and animal models demonstrated that cloning deletion, induction of anergy and immune suppression are the three major mechanisms of TRIM. In this article, the research advances on mechanism of TRIM and the mediators inducing TRIM are reviewed.
Animals ; Humans ; Immunomodulation ; Immunosuppression ; Platelet Transfusion ; adverse effects ; Transfusion Reaction

OBJECTIVETo analyze the clinical features of mid- and long-term acute cardiac allograft rejection to improve the long-term clinical outcomes of the patients.

METHODSFourteen recipients (11 males and 3 females) underwent orthotopic heart transplantation with standard immunosuppressive therapy protocols (3 cases) or induction therapy protocols (11 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as the maintenance immunosuppressive regimen. Acute graft rejection episodes occurred within 3 to 6 months in 1 case, within 6 months to 1 year in 3 cases, within 1 to 2 years in 3 cases, within 2 to 5 years in 6 cases, and above 5 years in 1 case.

RESULTSNo significant difference was found in the incidence of late heart rejection between the patients receiving the two immunosuppressive therapy protocols. Immunosuppressants were withdrawn or spared in 8 recipients due to different causes. Nine recipients with steroid-sensitive acute cardiac allograft rejection were treated with steroid-pulse therapy, while the other 5 were treated with a short course of polyclonal antithymocyte antibodies because of steroid-resistant acute rejection; in 11 cases, azathioprine was converted to mycophenolate mofetil. Four of the 5 late deaths occurred in the recipients with steroid-resistant rejection. The surviving recipients had a good quality of life, and no recurrent episodes of rejection or infection were observed in the follow-up period.

CONCLUSIONSLate acute cardiac allograft rejection is associated mainly with patient compliance but not with early immunosuppressive therapy protocols. The episodes are rather severe and should be timely treated with steroid pulses or polyclonal antithymocyte antibodies.

Adolescent ; Adult ; Cyclosporine ; Female ; Graft Rejection ; etiology ; prevention & control ; Heart Transplantation ; adverse effects ; Humans ; Immunosuppression ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; Young Adult