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When administered to mice, by various routes, two days before immunization with a tolerogenic dose (109) of sheep red blood cells, the immunosuppressive drug Cyclosporin A (CsA) prevents the suppression of delayed-type hypersensitivity (DTH) reactions. This was observed over a wide range of CsA doses (5-200 mg/kg), given, in a single dose, from a week before immunization to a day after, and with circulating CsA levels ranging below 45 ng/ml at the time of sensitization or challenge. The augmentation of DTH was characterized by induration, intense mononuclear cell infiltration, increased deposition of 125I-fibrin within the challenge site and was also reflected in in vitro assays of DTH. Cell transfer experiments showed that the CsA-enhanced DTH could be adoptively transferred to naive recipients, and suggested that CsA may be acting to inhibit a population of Ts cells normally effective during DTH, or to allow TH/TDTH cell priming. In addition, an increase in L3T4+ cells (TH/TDTH) was observed in the CsA-treated mice showing the break in suppression of DTH, suggesting that CsA allowed TH/TDTH cell priming. The augmented DTH reactions in CsA-treated mice were accompanied by profound inhibition of the production of splenic IgM antibody-producing cells and circulating anti-SRBC antibody levels. CsA was also shown to increase basal and mitogen-induced splenic macrophage procoagulant activity. These observations indicate that this model could prove useful in separation and study of cell-mediated and humoural immunity. In addition, they have important cautionary implications for the continuing investigation of the clinical potential of CsA.

There is a global programme of action in place for the protection of the marine environment to ensure our seas are clean and safe. One of the biggest threats to our oceans is man-made pollution and it is the responsibility of governments to conduct assessments to advise policy. Across the North-East Atlantic, Contracting Parties to the OSPAR Convention for the Protection of the Maine Environment of the North-East Atlantic, including the United Kingdom, are required to undertake monitoring and assessment of contaminants. The assessment utilises assessment criteria, including Background Assessment Concentrations (BAC) and Environmental Assessment Criteria (EAC). Guidelines for monitoring contaminants in biota include specific shellfish, flatfish and roundfish, as well as seabird eggs. Extending the assessment to other species has considerable merit, but such species may, for example, be more difficult to sample, with generic trophic level values obtained from literature and databases adding additional uncertainty to assessments. Currently, assessment criteria for organic and inorganic contaminants either do not account for secondary poisoning as a route of exposure, or a proxy is used due to the lack of ecotoxicological data available. Secondary poisoning is a result of biomagnification, which can be expressed as the trophic magnification factor (TMF; the average increase in concentration per trophic level). Fatty acid (FA) signatures and stable isotope (SI) ratios were used to develop an understanding of Scottish marine food web ecology and reliably ascribe trophic levels to a wide range of species. Analysis was conducted on 215 samples from different locations around Scotland which comprised of seven fish species, one shark species, fourteen marine invertebrate species, three marine mammal species and two zooplankton species. The concentrations of three priority heavy metals and six additional trace metals and metalloids, thirty-two PCB congeners and nine PBDE congeners were determined to investigate the relationship between concentration and potential influencing factors (trophic level, region, sample categorisation and physiological features). TMFs were calculated using two methods on selected PCB and PBDE congeners and metals and metalloids possessing a significant trophic relationship. It was concluded that ecosystem specific TMFs can be used as a reliable tool, permitting the assessment of a wider range of species, but a reasonable balance with respect to sample numbers of lower- versus higher-trophic level organisms is highly recommended when calculating TMFs.