No abstract

Dendritic cell (DC) subsets regulate alloimmune responses and may play a role in transplant tolerance. We extend an analysis of circulating precursors (p) of CD11c + CD123 −/lo (IL-3Ra −/lo ) (pDC1) and CD11c − CD123 hi (pDC2) DC subsets in primary cadaveric liver allograft recipients. Additionally, we examine DC subset levels in relation to the nature and extent of immunosuppressive therapy. The data consolidate the finding that the pDC2/pDC1 subset ratio is significantly higher in patients on minimal calcineurin inhibitor monotherapy undergoing successful weaning (n = 36) and in those off all anti-rejection therapy (n = 18) compared with patients on maintenance immunosuppression (n = 21). No relationship was found between the incidence of either pDC subset or the pDC subset ratio and time post-transplant or time off immunosuppression in any group. There was also no correlation between the pDC subset ratio and either prednisone or tacrolimus dose or tacrolimus trough blood level. No evidence was found that combination of these drugs influenced the incidence of pDC2 relative to pDC1. Thus, a greater prevalence of pDC2 in stable liver recipients on low dose anti-rejection therapy or in those off immunosuppression, compared with that in patients on maintenance immunosuppression, does not reflect a differential effect of anti-rejection drugs on pDC subsets.

Wildlife reintroductions to peopled landscapes pose socio-ecological opportunities and risks, and a responsibility to people as well as wildlife. Human–wildlife conflicts can escalate rapidly where anthropogenic foods and feeding cause wildlife to congregate and damage property. Those conflicts polarise attitudes to the wildlife and may cascade into conflicts between people over wildlife. The native parrot, kākā (Nestor meridionalis), was reintroduced to Wellington City in 2002 and we suspect that it initiated a classical human–wildlife conflict cascade. We tested for feeding-induced damage, and different attitude scores amongst neighbours using a postal household survey. We received 313 completed surveys, a 55.9% response rate, across eight suburbs. Minor to severe damage, costing up to NZ$3000 to repair, was reported to trees, buildings, and outdoor furniture. Seventeen respondents reported feeding kākā, mostly fruit and vegetables, but also sugar water, bread, and nuts and seeds, and we received surveys from 33 of their non-feeding neighbours. Feeding significantly increased reports of kākā, and kākā abundance was positively associated with kākā damage. Neighbourhoods closer to Zealandia (the wildlife sanctuary where kākā are fed) and the neighbours of people who fed kākā were statistically more likely to incur property damage than more distant suburbs and residents. Neighbours’ attitudinal scores about kākā and native birds were significantly negatively associated with greater kākā damage. The reintroduction of kākā has initiated a feeding-induced wildlife–human conflict. We discuss what can be learned from the experience with kākā in Wellington City for urban wildlife conservation in the future.

Summary von Willebrand factor (VWF) is a multimeric glycoprotein that mediates platelet adhesion and is decreased in von Willebrand disease (VWD). 1-8 deamino-d-arginine vasopressin (DDAVP), the most common treatment for VWD, is limited by tachyphylaxis and inconvenience, and in 20% of the patients, unresponsiveness. Recombinant human interleukin-11 (rhIL-11), a gp-130 signalling cytokine with haematopoietic and anti-inflammatory activity, increases VWF antigen and its activity in heterozygous VWF+/− mice and dogs. To determine the biological efficacy and safety of rhIL-11 in non-bleeding human subjects with mild VWD, we conducted a phase II prospective open-label trial of rhIL-11 at 10, 25 and 50 μg kg−1 subcutaneously (s.c.), given daily for 7 days in nine subjects with mild VWD. VWF and factor VIII (FVIII) levels increased gradually and progressively after s.c. rhIL-11, which was sustained through 7 days of dosing to 1.5- to 3-fold over baseline. Following intravenous DDAVP, 0.3 μg kg−1, on day 7 there was a further boost in VWF and FVIII levels, suggesting that the mechanism of rhIL-11 differs from that of DDAVP. Platelet VWF mRNA expression measured by quantitative PCR increased from two- to eightfold over baseline, suggesting that the mechanism of rhIL-11 effect may be upregulation of VWF mRNA. VWF and FVIII levels returned to baseline by day 14. rhIL-11 was well tolerated with less than grade-1 hypertension, hypokalaemia and fluid retention. Recombinant IL-11 increases VWF levels in humans with mild VWD, justifying future clinical trials to determine its potential in preventing or reducing bleeding in this patient population.

Dendritic cell (DC) subsets regulate alloimmune responses and may play a role in transplant tolerance. We extend an analysis of circulating precursors (p) of CD11c+ CD123−/lo (IL‐3Rα−/lo) (pDC1) and CD11c− CD123hi (pDC2) DC subsets in primary cadaveric liver allograft recipients. Additionally, we examine DC subset levels in relation to the nature and extent of immunosuppressive therapy. The data consolidate the finding that the pDC2/pDC1 subset ratio is significantly higher in patients on minimal calcineurin inhibitor monotherapy undergoing successful weaning (n = 36) and in those off all anti‐rejection therapy (n = 18) compared with patients on maintenance immunosuppression (n = 21). No relationship was found between the incidence of either pDC subset or the pDC subset ratio and time post‐transplant or time off immunosuppression in any group. There was also no correlation between the pDC subset ratio and either prednisone or tacrolimus dose or tacrolimus trough blood level. No evidence was found that combination of these drugs influenced the incidence of pDC2 relative to pDC1. Thus, a greater prevalence of pDC2 in stable liver recipients on low dose anti‐rejection therapy or in those off immunosuppression, compared with that in patients on maintenance immunosuppression, does not reflect a differential effect of anti‐rejection drugs on pDC subsets.