IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections.

IL-23 plays an important role in autoimmune tissue inflammation and induces the generation of not fully characterized effector cells that mediate protection against pathogens. In this paper, we established the essential role of IL-23R in the host response against intracellular pathogens. IL-23 was critical for the expansion or maintenance of gammadelta and double negative (DN) alphabeta T cells. These cells were rapidly recruited to the site of infection and produced large amounts of IL-17, IFN-gamma, and TNF-alpha. Notably, DN T cells transferred into L. monocytogenes-infected RAG2(-/-) mice prevented bacterial growth, confirming their protective role against intracellular pathogens. Our results show that IL-23 regulates the function of IL-17-producing gammadelta and DN T cells, two essential components of the early protective immune response directed against intracellular pathogens.

Bound residues: environmental solution or future problem?

The paper examines the issue of bound residues from the viewpoint of the risk assessment procedures employed for environmental protection. It considers, on one hand, the evidence that such residues are so tightly bound to soil organic matter as to be essentially unavailable; and on the other, the perspective that we should not be loading up the environment with compounds whose future behaviour and release we cannot predict. Existing knowledge of the mechanisms by which residues bind to soil organic matter suggests that release will be closely dependent on soil organic matter breakdown. Simple models of organic matter turnover suggest that the release following single applications of individual compounds will be very slow; but the significance of releases following repeated application over many years of a number of compounds needs to be investigated further. Applying environmental risk assessment techniques is complicated by the difficulty in identifying parent molecules and potential metabolites in the bound residue fraction. The paper concludes that for single additions of individual compounds, bound residues probably do represent an environmental solution. But the long-term significance of bound residues formed from multiple additions of a number of compounds is less clear. The paper recommends that future work should emphasise the biological significance of such residues and their release.

Prioritisation of veterinary medicines in the UK environment.

A wide range of veterinary medicines is used to treat animals in the UK. Whilst the environmental impact of selected substances (particulary the sheep dip chemicals, anthelmintics and fish farm chemicals) has been well studied, limited information is available in the public domain on the other groups of substances (e.g. antifungals, coccidiostats, antiprotozoals, hormones and growth promoters). There is therefore a need to identify other substances that may impact the environment in order to design national monitoring programmes, target experimental work and develop pollution prevention methodologies. In this study, a simple two-stage prioritisation scheme was developed and applied to veterinary medicines in use in the UK. In the first stage, those substances that have high potential to enter the environment in significant amounts were identified on the basis of amounts used in the UK, treatment type and metabolism. In stage 2, the hazard of the identified substances to terrestrial and aquatic organisms was assessed. Using the approach, a total of 56 substances or groups were assigned to a 'high priority' category. For eleven of these substances, sufficient data were available to characterise their risk, these were: oxytetracycline, chlortetracycline, tetracycline, sulphadiazine, amoxicillin, diazinon, tylosin, dihydrostreptomycin, apramycin, cypermethrin and sarafloxicin. For the remaining 45 substances, full datasets were not available and it is recommended that in the first instance, attempts are made to fill these data gaps.