ABSTRACT
Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host's defence to malaria. Transient receptor potential vanilloid 1 (TRPV1) modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 10(5) red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80(+)Ly6G(+) cell numbers as well as activation of both F4/80(+)and F4/80(+)Ly6G(+) cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1(+) and natural killer (NK) population, without interfering with natural killer T (NKT) cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.
Subject(s)
Capsaicin/analogs & derivatives , Plasmodium berghei/pathogenicity , TRPV Cation Channels/antagonists & inhibitors , Animals , Capsaicin/therapeutic use , Flow Cytometry , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-4/metabolism , Interleukin-6/metabolism , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Male , Mice , Mice, Inbred C57BL , Plasmodium berghei/immunologyABSTRACT
AIMS: This study evaluated the salivary biochemical and immunological status of children with cancer undergoing to antineoplasic treatment in an attempt to identify alternatives for a less invasive and less painful monitoring of these patients. MATERIALS AND METHODS: Unstimulated whole saliva samples were obtained from 115 children without cancer (control) and 32 children with cancer (CA). Children with cancer were also evaluated after antineoplasic treatment (CAT, n = 17). The salivary concentrations of glucose, triglycerides, total cholesterol, alkaline phosphatase, gamma-glutamyltransferase (GGT), urea, insulin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), levothyroxine (T4), and immunoglobulin A (IgA) were determined. RESULTS: Acute lymphocytic leukemia, acute myeloid leukemia, and Hodgkin's lymphoma were the most frequent cancers, although cases of non-Hodgkin's lymphoma, medulloblastoma, ependymoma, osteosarcoma, nephroblastoma, Ewing's sarcoma, and endodermal sinus tumor were also observed. The salivary concentration of cholesterol, triglycerides, or GGT did not differ between groups. Instead, the concentrations of alkaline phosphatase and T4 were higher in patients with cancer, irrespective of treatment. TSH levels were higher in the CA group and urea concentration was lower in the CAT group. T3 was undetectable in all groups. Antineoplasic treatment increased the glucose level and decreased the insulin concentration. Salivary concentration of total IgA was lower in children with cancer, irrespective of treatment. CONCLUSIONS: Cancer and antineoplasic treatment affected biochemical and immunological parameters in the saliva of children, shedding new light on the potential usefulness of saliva for monitoring children with cancer, especially to patients undergoing immunosuppressive therapy.
