Enhanced antigen presenting and T cell functions during late-phase allergic responses in the lung.

BACKGROUND: Allergic inflammation is a common feature of asthma and may contribute to both development and perpetuation of disease. The interaction of antigen-presenting cells (APC) with sensitized helper T lymphocytes (TC) producing Th2 cytokines may determine the inflammatory response. Recruitment of APC and TC to the lung during allergic responses has been demonstrated, but functional studies in humans have been limited. OBJECTIVE: This study examined the function of APC and TC accumulating at sites of inflammation after segmental allergen challenge (SAC). METHODS: Fifteen allergic patients underwent SAC, and cells from bronchoalveolar lavage (BAL) were collected after 24 hours. APC and TC from the blood and BAL were purified based on expression of the monocyte marker, CD14; the plasmacytoid dendritic cell (pDC) marker, BDCA4, identifying neuropilin-1 (NRP1); and the helper T cell marker, CD4. Functional activity was assessed using allergen-induced T cell proliferation. Flow cytometry identified cells expressing CD14 and NRP1. RESULTS: SAC resulted in a 12-fold increase in mononuclear cells having the morphologic appearance of blood monocytes. Most of these cells co-expressed CD14 and NRP1. After saline challenge, BAL mononuclear cells demonstrated little APC function. Following SAC, BAL mononuclear cells showed function equal to pDC from blood and greater than blood monocytes. Purified NRP1+ cells from BAL had even greater function than pDC cells from blood (P = .008). Using consistent sources of APC, enhanced proliferation of TC from lung compared to blood was also demonstrated (P = .002). CONCLUSIONS: The marked increase in APC function for allergen-specific TC proliferation during allergic inflammation is largely due to the recruitment of monocytes and dendritic cells. There is also an enhanced response in the lung TC population, consistent with recruitment of allergen-specific T cells. Interactions between recruited APC and TC may occur as an early event promoting allergic airway inflammation.

Pulmonary allergic responses augment interleukin-13 secretion by circulating basophils yet suppress interferon-alpha from plasmacytoid dendritic cells.

BACKGROUND: Allergic inflammatory processes may have the capacity to propagate systemically through the actions of circulating leucocytes. Consequently, basophils from allergic individuals are often 'primed', as evidenced by their hyperresponsiveness in vitro. IFN-alpha secreted predominantly by plasmacytoid dendritic cells (pDCs), suppresses basophil priming for IL-13 production in vitro. OBJECTIVE: This study sought in vivo correlates arising during experimental allergen challenge that support an 'axis-interplay' between basophils and pDCs. METHODS: Using segmental allergen challenge (SAC) in the lung, the immune responses of both cell types from the blood were investigated in volunteers (n=10) before and 24 h after allergen exposure. These responses were then correlated with inflammatory parameters measured in bronchoalveolar lavage fluids (BALF). RESULTS: In the blood, SAC significantly augmented IL-13 secretion by basophils induced by IL-3 (P=0.009), yet reduced IFN-alpha secreted by pDCs stimulated with CpG (P=0.018). Both parameters were negatively correlated (P=0.0015), at least among those subjects that secreted the latter. Circulating basophil IL-13 responses further correlated with post-SAC bronchoalveolar lavage (BAL) parameters including IL-13 protein (P=0.04), basophil (P=0.051), eosinophil (P=0.0018), and total cell counts (P<0.003). Basophil and IL-13 levels in BAL correlated likewise (P=0.0002). CONCLUSIONS: These results support a mechanism of immune regulation whereby an allergen reduces innate immune responses and IFN-alpha production by pDCs, resulting in an enhanced inflammation and basophil cytokine production at sites of allergen exposure.

Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects.

BACKGROUND: Systemic glucocorticoids are a major therapy for the management of allergic inflammation and asthma; however, information about their effects in vivo are limited. OBJECTIVE: This study was performed to examine the effects of prednisone on inflammatory mediators, cytokines, and cellular responses in the model of segmental allergen challenge (SAC) of allergic asthmatic subjects. METHODS: The effects of a 3-day pretreatment with oral prednisone (30 mg twice daily) on the physiologic and inflammatory responses to SAC were studied in 10 allergic asthmatic subjects in a double-blind, placebo-controlled, crossover protocol. RESULTS: Prednisone improved baseline FEV(1) by 10% and modestly inhibited the SAC-induced fall in FEV(1) at 30 minutes and at 6 to 8 hours. Five minutes after challenge, levels of histamine, PGD(2), 9alpha,11beta-PGF(2), and thromboxane B(2) increased in bronchoalveolar lavage fluid (median increase, 5- to 14-fold); prednisone did not inhibit these responses. Prednisone inhibited (median decrease, 66%-97%) the total influx of inflammatory cells, specifically eosinophils, basophils, and some subsets of T lymphocytes (CD4, CD45RA, and CD45RO cells) assessed 19 hours after SAC, but it did not inhibit the influx of neutrophils. Increases in soluble E-selectin, kinins, and albumin were also inhibited by the glucocorticoid (median decrease, 36%-74%). Prednisone treatment inhibited the appearance of mRNA, protein, or both for T(H)2 cytokines (IL-4 and IL-5), as well as for IL-2 and transforming growth factor alpha, but did not inhibit increases of immunoreactive GM-CSF in bronchoalveolar lavage fluid. CONCLUSION: These studies indicate that prednisone suppresses multiple components of allergic airway inflammation, including cell recruitment, adhesion molecule expression or release, airway permeability, and production of cytokines potentially involved in airway immunity or remodeling.

Perspectives for food research and European collaboration in the European Research Area and the new Framework Programme.

Since 1987, successive framework programmes have contributed to strengthen European food research through the establishment of networks between research institutions, universities and companies from various European countries. In the FAIR programme (1994-1998), 118 research projects comprising nearly 1,000 participants from the European Union and Associated States have been supported in the food area with a European funding of about [symbol: see text] 108 million. Within the Quality of Life and Management of Living Resources programme (1998-2002), food research is mostly supported within the key action 'food, nutrition and health' with a budget of [symbol: see text] 290 million. After the first four deadlines, 735 eligible research proposals have already been received. Further to their evaluation by a panel of independent experts, 108 proposals have been funded or selected for funding representing a total contribution of about [symbol: see text] 168 million. Among those, several clusters of projects are now running on important topics such as probiotics, coeliac diseases, mycotoxins, GMO, safety and food for the elderly. In addition, technology stimulation measures are largely benefiting SMEs to foster their innovation potential. In January 2000, the European Commission adopted a Communication entitled "Towards the European Research Area (ERA)" with the objective to contribute to developing better framework conditions for research in Europe. On 21 February 2001, the Commission adopted proposals to be submitted to the European Parliament and Council for the next framework programme for research and innovation (2002-2006). The new framework programme that is becoming one of the financial instruments of the ERA aims at catalysing the integration of European research by: strengthening of links between the Community research effort and national and regional research policies; concentrating on a limited number of priority fields or research to which activities at the Union level can add real value. One of the seven priority areas, entitled 'food safety and health risks', is intended to help establish the integrated scientific and technological bases needed to develop a system of production and distribution of safe and healthy food and control food-related risks, relying in particular on biotechnology tools, as well as health risks associated with environmental changes. A total budget of [symbol: see text] 600 million is proposed for this priority. In the priority areas, the new framework programme will work mainly by supporting the development of cooperation within networks of excellence bringing together the best research capabilities in Europe's regions to conduct common research programmes and integrated projects involving public and private partners, with clearly stated scientific and technological objectives.

Aftercare of psychiatric patients and its relation to rehospitalization.

In their study of the effects of posthospital treatment on psychiatric patients the authors found that those who entered aftercare were rehospitalized less often than those who did not. They found the rehospitalization rate was higher for schizophrenic patients than for patients in other diagnostic groups, and that schizophrenic patients who did not enter aftercare were rehospitalized at a higher rate than those who did. They found no difference between rehospitalization rates of patients who continued with their hospital therapist after discharge and those patients who worked with a new therapist.