Immunological parameters in prophylactic sublingual immunotherapy in asymptomatic subjects sensitized to Japanese cedar pollen.

BACKGROUND: This study aims to examine the immunological parameters, focusing IL-10 productivity, in prophylactic sublingual immunotherapy (SLIT) in asymptomatic subjects sensitized to Japanese cedar pollen (JCP). METHODS: This study was conducted as part of a randomized, double-blind, placebo-controlled, multiple center trial, and was performed for two consecutive pollen seasons in 2012 and 2013. The present results were based only on our institution. We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering. The SLIT group received standardized JCP extract for five months over the pollen season. We observed and judged development of the symptoms in the pollen season. The percentage of IL-10 producing CD4(+) T (Trl) cells, B cells and monocytes were analyzed by flow cytometry. JCP specific IgE and total IgE were also measured. RESULTS: The ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013. In 2012, the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group. In 2013, the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group. The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group. CONCLUSIONS: Prophylactic SLIT is effective for prevention of the development of pollinosis. Induction of IL-10 producing T cells, B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects.

Continuous high-dose antigen exposure preferentially induces IL-10, but intermittent antigen exposure induces IL-4.

IL-10 plays a critical role in the induction of specific T-cell tolerance. To date, whether IL-10 induction by antigen application is dose- or time-dependent remains unclear. In this study, IL-10 induction by allergen exposure was investigated in the several schedules. Oxazolone was repeatedly applied to mouse ear, and mRNA of inflammatory cytokines in lesional skins was measured. The results indicated that continuous high-dose antigen exposure induces IL-4 as well as abundant IL-10 production. Monocytes/dendritic cells and T cells are major source of IL-10. Allergen-specific immunotherapy is resumed before antigen scattering: preseason. We evaluated safe-loading dose of allergens in preseasonal therapy focusing Tr1 induction. Restarting immunotherapy with high dose effectively augmented IL-10 expression accompanied with further induction of IL-4 and inflammatory cytokines. Therefore, the protocol restarting with low-dose antigen is preferential to obviate the risk of exacerbation or anaphylaxis.

Improvement in early diagnosis of Japanese spotted fever by using a novel Rick PCR system.

Rickettsia diseases, including Japanese spotted fever (JSF), are serious infections. Delayed diagnosis occasionally results in life-threatening liver disorders and disseminated intravascular coagulation (DIC). Because of the shortness of the latent period, serological diagnosis is not preferable for early diagnosis of JSF. Until now, a polymerase chain reaction (PCR)-based diagnosis method has been used for early diagnosis, and the sensitivity reaches as high as 90% using skin biopsy samples as we previously reported. On the other hand, the sensitivity of the same PCR method using blood samples is limited at less than 50%. In the present study, using peripheral blood samples, we developed a novel diagnostic method for JSF using a Rick PCR system with original PCR primers, showing improved sensitivity compared with the conventional nested PCR. It may constitute a preferable diagnostic tool for early and sensitive diagnosis of Rickettsia infection.

Biologic therapy improves psoriasis by decreasing the activity of monocytes and neutrophils.

Therapy with monoclonal antibodies to tumor necrosis factor (TNF)-α and the interleukin (IL)-12/23 p40 subunit has significantly improved the clinical outcome of patients with psoriasis. These antibodies inhibit the effects of the target cytokines and thus the major concern during their use is the induction of excessive immunosuppression. Recent studies evaluating the long-term efficacy and safety of biologic therapy in psoriasis have shown no significant appearance of serious adverse effects including infections and malignancies. However, the immunological consequence and the mechanism by which the blockade of a single cytokine by biologics can successfully control the activity of psoriasis remain unclear. In the current study, we investigated the effect of biologic therapy on cytokine production of various lymphocytes and on the activity of monocytes and neutrophils in psoriatic patients. Neutrophils, monocytes and T cells were purified from heparinized peripheral venous blood by Ficoll density gradient centrifugation, and γ-interferon, TNF-α and IL-17 production from lymphocytes was measured by flow cytometer. The activation maker of neutrophils and the activated subsets of monocytes were also analyzed. Biologic therapy induced no significant changes in the cytokine production by lymphocytes from the skin and gut-homing T cells. However, neutrophil activity and the ratio of activated monocyte population increased in severely psoriatic patients were normalized in psoriatic patients receiving biologic therapy. The present study showed that biologic therapy ameliorates clinical symptoms and controls the immune response in patients with psoriasis.