Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis.

T lymphocyte-expressing natural killer (NK) cell markers (NKT cells) play a role in immune regulation. Our aim was to evaluate the in vivo effect of adoptive transfer of immune-programmed NKT cells. Colitis was induced in C57/B6 mice by 2,4,6-trinitrobenzenesulfonic acid. NKT, CD4, CD8 lymphocytes, and dendritic cells (DC) were prepared from spleens of naive mice, animals with colitis, and animals with colitis that were orally tolerized. Subsets of splenocytes, NKT, CD4, and CD8 and NKT+CD4, NKT+CD8, and NKT+DC lymphocytes were prepared. Assessment of the T helper cell type 1 (Th1)/Th2 cytokine secretion paradigm in vitro was performed before and following exposure to the antigen. Adoptive transfer of ex vivo immune-programmed lymphocytes from each group was performed into recipient mice, followed by colitis induction. Ex vivo exposure of NKT cells harvested from mice with colitis-to-colitis proteins [colitis-extracted proteins (CEP)] led to a Th2 cytokine shift. The interleukin (IL)-4/interferon-gamma (IFN-gamma) ratio increased for NKT harvested from colitis-harboring mice following exposure to CEP. Adoptive transfer of NKT lymphocytes harvested from colitis-harboring mice, which were ex vivo-educated, significantly alleviated experimental colitis in vivo. Intrahepatic NKT lymphocytes increased significantly in mice transplanted with NKT lymphocytes harvested from colitis-harboring donor mice, which were ex vivo-exposed to CEP, similar to mice transplanted with NKT lymphocytes harvested from tolerized donors. Exposure of NKT cells to the disease-target antigen induced a significant increase in the IL-4/IFN-gamma cytokine ratio. Adoptive transfer of a relatively small number of immune-programmed NKT cells induced a systemic Th1 to Th2-immune shift and alleviated immune-mediated colitis.

A Randomized Controlled Study to Determine the Efficacy of Garlic Compounds in Patients With Hematological Malignancies at Risk for Chemotherapy-Related Febrile Neutropenia.

BACKGROUND: Patients receiving chemotherapy for hematological malignancies are at high risk for febrile neutropenia (FN). Garlic extracts (GEs) are natural food substances showing antimicrobial effects in vivo. OBJECTIVES: We explored whether adding GE may be efficacious in reducing the risk or severity of infections. DESIGN: This was a placebo-controlled double-blind randomized study. RESULTS: Of 95 patients randomized to receive GE or placebo following chemotherapy, a febrile episode was documented in 50% of patients receiving GE and 63.3% receiving placebo (P = .89). There was a higher risk of developing a third and fourth febrile episode in the GE group (P = .01). However, among those at a lower risk for FN, those receiving GE developed fewer FN episodes (P = .075), especially those with severe neutropenia (P = .05). Major adverse events were distributed equally, but nonadherence was more common in the GE than in the placebo group: 19.5% versus 4%, respectively (P = .05). CONCLUSIONS: GE was safe and did not reduce FN risk in the entire cohort, but yet appeared to exert a protective effect in the lower-risk subgroup. We do not recommend the use of GE for FN prevention in higher-risk patients. A larger-scale clinical trial for the lower-risk subgroup of patients is advocated. (This trial was registered at www.clinicaltrials.gov as NCT00247039.).

Intrauterine balloon tamponade as a treatment for immune thrombocytopenic purpura-induced severe uterine bleeding.

OBJECTIVE: To report our experience of applying balloon tamponade in the treatment of intrauterine bleeding in two patients with immune thrombocytopenic purpura (ITP). Immune thrombocytopenic purpura is a well-known hematologic autoimmune disease. The uterus may be a major site of bleeding in patients with ITP. Halting bleeding is imperative to reduce blood loss and platelet consumption and to allow medical treatment to increase platelet count. Balloon tamponade has been described as an effective method to control bleeding in a variety of clinical situations; it is an effective and accessible modality, requiring no analgesia or anesthesia, and helps facilitate continuous monitoring of uterine bleeding. DESIGN: Report of two cases. SETTING: Obstetrics and gynecology department in a tertiary care center in Jerusalem, Israel. PATIENT(S): Two patients with ITP with severe uterine bleeding refractory to treatment with estrogen and IV IgG. INTERVENTION(S): Intrauterine balloon tamponade. MAIN OUTCOME MEASURE(S): Cessation of uterine bleeding, appearance of complications. RESULT(S): Insertion of balloon tamponade successfully controlled bleeding in both cases. The patient in case 1 subsequently had persistent hypomenorrhea. The patient in case 2 had abdominal pain and suspected pelvic inflammation. CONCLUSION(S): Our presented cases demonstrate that uterine bleeding can be controlled successfully in patients with ITP with an intrauterine balloon. This novel application raises many technical issues, such as the appropriate filling pressures and duration of treatment. Possible risks, such as endometrial injury, still remain to be resolved and mandate future clinical research.