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Background Immunomodulatory agents that induce antitumor immunity have great potential for treatment of cancer. We have previously shown that interleukin (IL)-31, a proinflammatory cytokine from the IL-6 family, acts as an antiangiogenic agent. Here, we characterize the immunomodulatory effect of IL-31 in breast cancer.Methods In vivo breast carcinoma models including EMT6 and PyMT cell lines were used to analyze the effect of IL-31 on the composition of various immune cells in the tumor microenvironment using high-throughput flow cytometry. In vitro studies using isolated cytotoxic T cells, CD4+ T cells, myeloid-derived suppressor cells (MDSCs) and macrophages were carried out to study IL-31 immunological activity. The generation of recombinant IL-31 bound to IgG backbone was used to test IL-31 therapeutic activity.Results The growth rate of IL-31-expressing breast carcinomas is decreased in comparison with control tumors due, in part, to antitumor immunomodulation. Specifically, cytotoxic T cell activity is increased, whereas the levels of CD4+ T cells, MDSCs, and tumor-associated macrophages are decreased in IL-31-expressing tumors. These cellular changes are accompanied by a cytokine profile associated with antitumor immunity. In vitro, IL-31 directly inhibits CD4+ Th0 cell proliferation, and the expression of Th2 canonical factors GATA3 and IL-4. It also promotes CD8+ T cell activation through inhibition of MDSC activity and motility. Clinically, in agreement with the mouse data, alterations in immune cell composition in human breast cancer biopsies were found to correlate with high expression of IL-31 receptor A (IL-31Ra) . Furthermore, high coexpression of IL-31Ra, IL-2 and IL-4 in tumors correlates with increased survival. Lastly, to study the therapeutic potential of IL-31, a recombinant murine IL-31 molecule was fused to IgG via a linker region (IL-31-L-IgG). This IL-31-L-IgG therapy demonstrates antitumor therapeutic activity in a murine breast carcinoma model.Conclusions Our findings demonstrate that IL-31 induces antitumor immunity, highlighting its potential utility as a therapeutic immunomodulatory agent.

Background: One aspect of ordering and prescribing medication is the requirement for a trained professional to review medication orders or prescriptions for appropriateness. In practice, this review process is usually performed by a clinical pharmacist. However, in many medical centers there is a shortage of staff and a pharmacist is not always available.Objective: To determine whether remote review of medication orders by a pharmacist is a plausible method in a pediatric intensive care unit (PICU). Methods: A pharmacist from the pharmacy department reviewed medication orders of patients admitted to our PICU over a 7-month period for appropriateness. A special form for medical orders was filled in and sent to the physician in the PICU, who replied informing whether the recommendation had been accepted. The time spent by the pharmacist for this activity was recorded.Results: The review time for one medical record was 8.9 (95% CI, 6.9-10.9) minutes. Every additional drug prescribed increased the total review time by 0.8 (95% CI, 0.45-1.11) minutes. The pharmacist filled in 186 forms on 117 admissions for 109 children. The median review time was 15 (12.8-18.8) and 12 (9-15) minutes, respectively, for patients with psychiatric-neurologic disorders compared to those without (p=0.032). Usually, a daily workload of 240 minutes was needed for the pharmacist accompanying the round in contrast to 108 minutes per day needed to review all the medical records in 95% of the cases. The physician accepted 51.2%, rejected 11.9% and made no comment on 36.9% of the recommendations. Conclusion: Hospitals facing budget shortages can carry out focused remote reviews of prescriptions by the pharmacist.