Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease

We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus(EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis(HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease(IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Immunomodulatory therapy for the management of critically ill patients with COVID-19:A narrative review

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of the ongoing coronavirus disease 2019(COVID-19)pandemic.Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies.AIM To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets.METHODS A comprehensive literature search was developed.Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate.Finally,a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed.This recommendation was made based on the consensus of all the authors.RESULTS A brief rationale on the SARS-CoV-2 pathogenesis,immune response,and inflammation was developed.The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed.Finally,based on the level of scientific evidence,a recommendation was established for each of them.CONCLUSION Although several promising therapies exist,only the use of corticosteroids and tocilizumab(or sarilumab in absence of this)have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19.Endotypes including both,clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.

Role of 1, 25-dihydroxyvitamin D3 in preventing acute rejec tion of allograft following rat orthotopic liver transplantation

Background We investigated the role of 1, 25-dihydro xyvitamin D3 (1, 25-(OH) 2D 3) in preventing allograft from acute rejection following orthotopic liver transplantation. Methods A rat orthotopic liver transplantation model was used i n this study. SD-Wistar rats served as a high responder strain combination. Recipients were subjected to administration of 1, 25-(OH) 2 D 3 at dosages ranging from 0.25 μg·kg -1 ·d -1 to 2.5 μg·kg -1 ·d -1 . Survival a fter transplantation as well as pathological rejection grades and IFN-γ mRNA, IL-10 mRNA transcription intragraft on day 7, and day 30 post-transplantation were observed. Results After recipients were treated with 1, 25(OH) 2 D 3 at dosages of 0.5 μg·kg -1 ·d -1 or 1.0 μ g ·kg -1 ·d -1 , survivals of recipients were prolonged. Ninety-five percent confidence intervals of survival were 46-87 days and 69-102 days (both P=0.0005 vs control group), respectively. On day seven post-transplantation, relative levels of IFN-γ mRNA transcription were 0.59±0.12 and 0.49±0.16, which was higher t han the control group (P=0.005, P=0.003, respectively). Relative leve ls of IL-10 mRNA transcription were 0.83±0.09 and 0.76±0.09, which was lower than the con trol group (P=0.002, P=0.003, respectively). At a dosage of 0.5 μg·kg -1 ·d -1 , the median of pathological rejection gra de on day seven and on day thirty post-transplantation were 1.5 and 2.0 in comparison with the CsA-treated g roup (P=0.178, P=0.171, respectively). At a dosage of 0.5 μg·kg -1 ·d -1 , the median of pathological rejection grade on day seven and day thirty post-transplantation were 1.5 and 1.5 in comparison with CsA-treated group (P=0.350, P=0.69 3, respectively).Conclusion After each recipient was treated with 1,25-(OH) 2 D 3 at a dosage of (0.5-1.0) μg·kg -1 ·d -1 , transcription of cytokine intragraft was accommodated effectively and deviated to Th2 type, resulting in alleviation of acute rejection. 1, 25-(OH) 2 D 3 can prolong survival of recipient after orthotopic liver transplantation.

Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity

Objective To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.Methods Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis.Results CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18. 3±4. 6 vs 4. 8±1.3 cells/mm2, P < 0. 05 ) . In comparision with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0. 12 ±0. 03 vs 0. 22±0. 02 ml ·min-1·100g-1 body weight, P < 0. 05), tubular injury (2. 29 ±0. 43 vs 1. 42±0. 26, P < 0. 05), and interstitial fibrosis (2. 83±0. 20 vs 1. 46±0. 19, P <0. 05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18. 3±4. 6 vs 7. 7±2.1 cells/mm2, P<0. 05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P<0. 05).Conclusion These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.