We studied the in vitro effects of butyric acid on differentiation, maturation and function of dendritic cells (DC) and macrophages (M(Phi)) generated from human monocytes. A non-toxic dose of butyrate was shown to alter the phenotypic differentiation process of DC as assessed by a persistence of CD14, and a decreased CD54, CD86 and HLA class II expression. The more immature differentiation stage of treated cells was confirmed further by their increased phagocytic capability, their altered capacity to produce IL-10 and IL-12, and their weak allostimulatory abilities. Butyrate also altered DC terminal maturation, regardless of the maturation inducer, as demonstrated by a strong down-regulation of CD83, a decreased expression of CD40, CD86 and HLA class II. Similarly, butyrate altered M(Phi) differentiation, down-regulating the expression of the restricted membrane antigens and reducing the phagocytic capacity of treated cells. To investigate further the mechanism by which butyrate hampers the monocyte dual differentiation pathway, we studied the effects of 1,25(OH)2D3 alone or in combination with butyrate on the phenotypic features of DC. Unlike 1,25(OH)2D3, butyrate inhibited DC -differentiation without redirecting it towards M(Phi). Combined treatment gave rise to a new cell subset (CD14(high), CD86 and HLA-DR(low)) phenotypically distinct from monocytes. These results reveal an alternative mechanism of inhibition of DC and M(Phi) differentiation. Altogether, our data demonstrate a novel immune suppression property of butyrate that may modulate both inflammatory and immune responses and support further the interest for butyrate and its derivatives as new immunotherapeutic agents.

IntroductionIn B-cell chronic lymphocytic leukemia (B-CLL), treatment must be instituted for advanced (ie, B and C) stage patients. 1 Because the duration of response is correlated to the response rate, 2,3 autologous stem cell transplantation has been tested in the disease 2,4-6 with encouraging results. Therefore, ongoing cooperative studies are evaluating autologous peripheral blood stem cell (PBSC) transplantation at the time of first remission. To obtain the best response before PBSC harvest, fludarabine (FDR) is considered the most efficient drug in the treatment of B-CLL and is increasingly used as frontline therapy. 7,8 An oral formulation of this drug is available. 9 The adjunction of cyclophosphamide 10,11 (CY) or rituximab and CY 12 with FDR appears still more efficient and could lead to molecular remissions.However, it has been suggested that occasionally in B-CLL 13-15 and in other disorders, [16][17][18][19] FDR could adversely affect PBSC mobilization. Conversely, high CD34 cell yields can be obtained in B-CLL patients treated with non-FDR-containing regimens. 20 This controversial issue has never been prospectively evaluated in a large number of B-CLL patients in first remission. The aim of this prospective study was to evaluate steady state filgrastim-or lenograstim-primed PBSC mobilization in 38 B-CLL patients in first remission after oral frontline treatment with FDR-CY. Study design PatientsThe study involved 38 patients with B-CLL (median age, 53.5 years [range, 38-66 years]; 33 men, 5 women) in complete remission (CR) (n ϭ 26) or partial remission (PR) (n ϭ 12), according to the National Cancer Institute criteria, 21 after frontline treatment with FDR-CY. All gave informed consent. They had been previously enrolled in a clinical trial (ME 98123 Schering S.A.) that evaluated the efficacy and safety of 6 monthly courses of FDR (30 mg/m 2 per day) and CY (200 mg/m 2 per day) both given orally for 5 consecutive days. 11 All these patients (34 stage B and 4 stage C) had received 6 FDR-CY courses, except 4 who had received either 5 courses (n ϭ 2), 4 courses (n ϭ 1), or 2 courses plus 3 courses of a CHOP-like regimen (n ϭ 1) because of toxicity. After evaluation performed 2 months after the last FDR-CY course, responding patients were considered for PBPC collection at the time of first CR or PR. According to the aforementioned trial, high-dose therapy should not be performed before relapse. Mobilization and apheresisMobilization was initiated at least 2 months after the last FDR-CY course, according to published results. 13 To collect a number of CD34 cells equaling at least 2.0 ϫ 10 6 /kg body weight, all patients underwent a first steady state PBSC mobilization using either filgrastim (10 g/kg per day) or lenograstim (7 g/kg per day) given once a day for 4 to 6 consecutive days until adequate blood CD34 circulation was achieved. Apheresis was initiated when circulating CD34 cell levels reached 10 ϫ 10 6 /L. Two to 3 blood mass volume was processed during each apheresis performed with continuou...

In our pediatric series, combined medical (corticosteroids, elemental diet, and food elimination diet) and endoscopic approach (repeated balloon dilation) were effective and safe in patients with severe EoE and esophageal stricture.

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Transient, isolated hyperphosphatasemia is a rare, benign condition of childhood. Few cases have been described in transplant patients. We report six cases: three after liver transplantation and three after kidney transplantation. Such a phenomenon was found to be as benign after organ transplantation as it is in healthy children. Hence, an isolated increase in the serum alkaline phosphatase level following transplantation should not be of concern in this population of patients.

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