Local cytomegalovirus infection in patients with diarrhea following allogeneic stem cell transplantation.

To evaluate local cytomegalovirus (CMV) infection in patients who developed diarrhea after allogeneic hematopoietic stem cell transplantation (HSCT), histologic and molecular analysis was carried out with intestinal biopsy samples. from 17 transplant recipients. A CMV-specific intranuclear inclusion body indicating intestinal CMV disease was documented in 2 biopsy samples. CMV DNA was detected by quantitative polymerase chain reaction in 8 of 23 (34.8%) samples, including 2 samples diagnosed with intestinal CMV disease. Of 15 patients without histologic confirmation of intestinal CMV disease, pre-emptive therapy was carried out for 8 patients based on positive antigenemia, and for 2 patients on positive CMV DNA, respectively. Intestinal CMV disease was successfully treated with antiviral therapy for 2 patients and prevented with pre-emptive therapy based on either positive antigenemia or positive CMV DNA for 10 patients. Endoscopic examinations with histologic and molecular analysis may be important in the early treatment and the prevention of intestinal CMV disease in patients with diarrhea after allogeneic stem cell transplantation.

Association between IFNA genotype and the risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by multisystem inflammation and production of autoantibodies, which can generate immune complexes and may cause tissue damage through the recognition of an autoantigen. Although many factors have been proposed, such as genetic factors, environmental factors, hormonal action, viruses, and dysregulation of cytokine production, the cause of this disease is not well understood. It has been reported that the levels of interferon (IFN)-alpha in the sera of some SLE patients are elevated and that IFN-alpha induces maturation of monocytes into highly active antigen-presenting dendritic cells (DCs). We analyzed the association between IFN-alpha genotype and the risk of SLE to clarify whether IFN-alpha plays a central role in susceptibility to SLE. The results showed that no IFN-alpha genotype was significantly associated with the risk of SLE.

Novel regulatory mechanisms of CD40-induced prostanoid synthesis by IL-4 and IL-10 in human monocytes.

Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE(2), a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE(2) via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE(2) production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-kappaB. Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-kappaB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-kappaB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.