Comparative proteomic study reveals the enhanced immune response with the blockade of interleukin 10 with anti-IL-10 and anti-IL-10 receptor antibodies in human U937 cells.

Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes.

Iodine-125 labeled Australian frog tree host-defense peptides caerin 1.1 and 1.9 better inhibit human breast cancer cells growth than the unlabeled peptides. 125I-caerin 1.9 may better be used for the treatment of breast cancer.

OBJECTIVE: We recently showed that host defense caerin peptides isolated from Australian frog tree were able to inhibit cervical cancer tumour cell growth in vitro. We wished to determine if radioactive isotope iodine-125 (125I) can be labeled to caerin 1.9 peptide and if this peptide is bioactive for breast cancer cells treatment. SUBJECTS AND METHODS: The biological function of caerin (1.1 and 1.9) peptides were investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The anti-cancer effect of 125I labeled caerin 1.9 was compared with unlabeled caerin 1.9 peptide. The tissue distribution of 125I labeled caerin 1.9 peptide was further studied in mice. RESULTS: In the current paper, we demonstrated that caerin peptides (1.1 and 1.9) were separately able to inhibit the viability of two breast cancer cell lines in vitro and this inhibition was more profound when these peptides were simultaneously applied. Moreover, 125I can be stably attached to caerin 1.9 peptide with high efficiency. Iodine-125 labeled caerin 1.9 inhibited breast cancer cells line MCF-7 viability more efficiently than free 125I and also than unlabeled caerin 1.9. Additionally, iodine-125 labeled caerin 1.9 in vivo imaging demonstrated that although slightly, it could be accumulated in tumor tissue. CONCLUSION: Our results from this totally original study indicated that radioactive isotope 125I labeled to caerin peptide 1.9 may be used to treat breast cancer while at the same time the response to treatment may be monitored by simultaneous imaging.

Genital warts treatment: Beyond imiquimod.

Genital warts are one of the most common sexually transmitted diseases worldwide. The disease is a result of infection with low-risk types of human papillomaviruses, mostly type 6 and 11. Current therapies for genital warts are mainly ablative, or alternatively topical application of imiquimod cream and sinecatechin (polyphenon E) ointment to the warts. However, low patient compliance and high recurrence rate are significant problems for the treatment of genital warts by imiquimod and ablative therapies. We summarise recent literature in this area and propose combining imiquimod with other therapies to increase the efficacy of imiquimod.

Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice.

BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine. METHODS: We investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model. RESULTS: We now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice. CONCLUSIONS: Our results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer.