Abstract:Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-␥ (IFN-␥)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-␥ production by murine splenocytes

Despite the potential for patient-reported outcome measures (PROMs) and experience measures (PREMs) to enhance understanding of patient experiences and outcomes they have not, to date, been widely incorporated into renal registry datasets. This report summarizes the main points learned from an ERA-EDTA QUEST-funded consensus meeting on how to routinely collect PROMs and PREMs in renal registries in Europe. In preparation for the meeting, we surveyed all European renal registries to establish current or planned efforts to collect PROMs/PREMs. A systematic review of the literature was performed. Publications reporting barriers and/or facilitators to PROMs/PREMs collection by registries were identified and a narrative synthesis undertaken. A group of renal registry representatives, PROMs/PREMs experts and patient representatives then met to (i) share any experience renal registries in Europe have in this area; (ii) establish how patient-reported data might be collected by understanding how registries currently collect routine data and how patient-reported data is collected in other settings; (iii) harmonize the future collection of patient-reported data by renal registries in Europe by agreeing upon preferred instruments and (iv) to identify the barriers to routine collection of patient-reported data in renal registries in Europe. In total, 23 of the 45 European renal registries responded to the survey. Two reported experience in collecting PROMs and three stated that they were actively exploring ways to do so. The systematic review identified 157 potentially relevant articles of which 9 met the inclusion criteria and were analysed for barriers and facilitators to routine PROM/PREM collection. Thirteen themes were identified and mapped to a three-stage framework around establishing the need, setting up and maintaining the routine collection of PROMs/PREMs. At the consensus meeting some PROMs instruments were agreed for routine renal registry collection (the generic SF-12, the disease-specific KDQOL™-36 and EQ-5D-5L to be able to derive quality-adjusted life years), but further work was felt to be needed before recommending PREMs. Routinely collecting PROMs and PREMs in renal registries is important if we are to better understand what matters to patients but it is likely to be challenging; close international collaboration will be beneficial.

Endotoxin tolerance, the transient, secondary down-regulation of a subset of endotoxin-driven responses after exposure to bacterial products, is thought to be an adaptive response providing protection from pathological hyperactivation of the innate immune system during bacterial infection. However, although protecting from the development of sepsis, endotoxin tolerance also can lead to fatal blunting of immunological responses to subsequent infections in survivors of septic shock. Despite considerable experimental effort aimed at characterizing the molecular mechanisms responsible for a variety of endotoxin tolerance-related phenomena, no consensus has been achieved yet. IL-12 is a macrophage- and dendritic cell (DC)-derived cytokine that plays a key role in pathological responses to endotoxin as well as in the induction of protective responses to pathogens. It recently has been shown that IL-12 production is suppressed in endotoxin tolerance, providing a likely partial mechanism for the increased risk of secondary infections in sepsis survivors. We examined the development of IL-12 suppression during endotoxin tolerance in mice. Decreased IL-12 production in vivo is clearly multifactorial, involving both loss of CD11chigh DCs as well as alterations in the responsiveness of macrophages and remaining splenic DCs. We find no demonstrable mechanistic role for B or T lymphocytes, the soluble mediators IL-10, TNF-α, IFN-αβ, or nitric oxide, or the NF-κB family members p50, p52, or RelB.

Worldwide, it is estimated that there are more than 100.000 infants born with congenital rubella syndrome (CRS) each year. In 1998, standard case definitions for surveillance of CRS and rubella were developed by the World Health Organization (WHO). In 2001, 123 countries/territories reported a total of 836.356 rubella cases. In the future more countries are expected to report on rubella as a global measles/rubella laboratory network is further developed under the coordination of WHO. Operational research is being conducted to improve rubella surveillance. This includes projects on initiating CRS surveillance, comparative studies on diagnostic laboratory methods, and molecular epidemiology research to expand the global understanding of patterns of rubella virus circulation. In 1996 a WHO survey found that 78 od 214 reporting countries/territories (36%) were using rubella vaccine in their routine immunization services. By the en of 2002 a total of 124 of the 214 counties/territories (58%) were using rubella vaccine. Rubella vaccine use varies by stage of economic development: 100% for industrialized countries, 71% for countries with economies in transition, and 48% for developing countries. A safe effective rubella vaccine is available, and there are proven vaccination strategies for preventing rubella and CRS. A WHO position paper provides guidance on programmatic aspects of rubella vaccine introduction. The introduction of rubella vaccine is cost-effective and cost-beneficial but requires ongoing strengthening of routine immunization services and surveillance systems.

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