Biomedical subjects

Nina Ivanovska

Publications and source records attributed to Nina Ivanovska.

7 recordsLinked to original sources

PubMed2006

Influence of leflunomide on gastrointestinal Candida albicans infection induced in naive and arthritic newborn mice.

Mucosal Candida albicans infection in immunocompromised individuals being treated with recently advanced drugs can progress to systemic disease. One such medication applied in patients with rheumatoid arthritis is leflunomide. The object of the present study was to investigate the effect of leflunomide on a model of gastrointestinal (g.i.) C. albicans infection induced in naïve or arthritic mice and on the host resistance to systemic re-infection. Newborn mice were orally inoculated with 1 x 10(5) colony forming units (CFU) of C. albicans and at age of 5 weeks they were treated with 5 mg/kg or 20 mg/kg of leflunomide for 10 consecutive days. Both doses elevated the yeast colonization of the stomach, without the dissemination into the internal organs. This was in parallel with the enhanced delayed type hypersensitivity (DTH) reaction to the yeast. Contrary to that, leflunomide caused a shift to Th2 reactivity by prevalence of IL-4 to IFN-gamma and a suppression of anti-Candida antibody synthesis by a higher dose. It might be supposed that infection increased autoimmune response in arthritic mice, according to stimulated DTH reaction to collagen. The administration of leflunomide during the simultaneous development of infection and arthritis diminished anti-Candida and anti-collagen antibody synthesis compared to untreated infected arthritic mice. The improved survival of arthritic infected animals against severe systemic re-infection was not changed after administration of leflunomide to re-infected arthritic mice. We can conclude that although leflunomide influenced cytokine secretion and suppressed anti-Candida antibody production it neither provokes a progression from gastrointestinal to systemic C. albicans infection nor increases the susceptibility to severe C. albicans re-infection of arthritic mice.

Animals↗

PubMed2006

Host resistance to Candida albicans infection of mice with collagen-induced arthritis treated with leflunomide.

The dehydro-orotate dehydrogenase inhibitor leflunomide is used for the treatment of rheumatoid arthritis. In the present study, its influence on host resistance to Candida albicans infection in mice with collagen-induced arthritis (CIA) was investigated. Leflunomide administered at a dose of 5 mg/kg for 5 consecutive days in mice with CIA inhibited collagen-specific cellular and humoral responses. The drug did not change the severity of primary C. albicans infection evaluated by kidney and liver colonization. At the early stage of infection leflunomide inhibited IFN-gamma production and enhanced IL-4 secretion. The effect of the drug on IL-4 production was less pronounced at the late phase of infection. Leflunomide enhanced anti-Candida IgM antibody production and diminished anti-Candida IgG antibody synthesis. This correlated with impaired resistance to reinfection. Results demonstrate that leflunomide administration to mice with collagen-induced arthritis might affect mechanisms of the late immune response to C. albicans infection.

Animals↗

PubMed2005

Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus.

Killed viral vaccines are known to induce primarily antibody responses. By contrast DNA vaccination using naked DNA encoding viral antigens induces both humoral and cellular immune responses. Various approaches have been used to construct DNA vaccines with build-in adjuvanticity. We hypothesized that sequences encoding a common epitope of influenza A virus hemagglutinin jointed to sequences encoding a single-chain variable fragment (scFv) antibody fragment to a costimulatory B cell surface receptor would result in the in vivo expression of a chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule was constructed by us, encoding a T and B cell epitope-containing influenza hemagglutinin peptide and a scFv antibody fragment binding to mouse complement receptors I and II (CR1 and CR2). A single immunization with a plasmid containing the described construct induced a strong anti-influenza cytotoxic response lasting for more than six months and a weak antibody response.

Adjuvants, Immunologic↗

PubMed2005

Candida albicans double-stranded DNA can participate in the host defense against disseminated candidiasis.

In the present work, we studied the in vitro immunomodulatory properties of double-stranded Candida albicans DNA and its protective effect in murine disseminated candidiasis. DNA induced the production of TNF-alpha by peritoneal macrophages and splenocytes in vitro through a chloroquine-dependent mechanism. Yeast DNA acted synergistically with IFN-gamma in triggering the secretion of nitric oxide by macrophages and enabled them to stimulate the proliferation of T cells in response to soluble anti-CD3. The effect of DNA on splenocytes is associated with an enhanced synthesis of IFN-gamma, IL-2 and IL-10. In vivo, DNA decreased the mortality and lowered the kidney contamination in mice intraperitoneally inoculated with C. albicans simultaneously with an increase in the specific proliferative response and cytokine production. The present results indicate that C. albicans DNA can provide protection against disseminated infection.

Animals↗

PubMed2004

Inflammation induced by inoculation of the joint with Candida albicans.

In humans Candida albicans is the most frequently isolated opportunistic fungal pathogen. In immunocompromized host the balance with the commensal fungus easily turns to life-threatening disseminated infection. The asymptomatic Candida persistence in organs and the recurrent infections suggest continuous circulation of yeast cells and their degradation products. Under certain conditions, joints might become one of the infectious sites. More easily a reactivation and destructive process can be provoked in individuals with established arthritis. We have investigated the joint inflammation caused by inoculation of the paw with live C. albicans, in intact mice and mice with collagen-induced arthritis (CIA). The results demonstrate that C. albicans infection when localized into the joints caused rapidly progressing septic arthritis. The effect was associated with a strong swelling, a rapid influx of polymorphonuclear (PMN) cells, and an elevated secretion of TNF-alpha and IFN-gamma by lymph node cells. Joint infection exacerbated the established CIA which correlated with an increased level of anti-collagen antibodies.

Animals↗

PubMed2003

Single immunization of newborn mice with heterologous type-II collagen induces arthritic disease.

Collagen-induced arthritis (CIA) is a widely accepted model of autoimmune disease with significant similarities to rheumatoid arthritis in humans. CIA is provoked in susceptible strains upon immunization of adult mice with native type-II collagen in complete Freund's adjuvant (CFA). Neonatal exposure to antigen is supposed to result in T cell clone deletion and induction of tolerance. Here we report that the neonatal injection of bovine type-II collagen (bCII) to ICR (CD-2) mice triggers the development of autoimmune chronic joint inflammation. Compared with standard CIA significant joint swelling was not observed and anti-collagen antibodies were not detected if the second challenge with the antigen was not supplied. Histopathologic examination of the joints showed cell infiltration, synovial hyperplasia and at the later period bone destruction. Mice immunized as neonates expressed Ag-specific proliferative response and delayed type hypersensitivity (DTH) reaction to bCII.

Animals↗

PubMed2002

Host resistance against Candida alibcans infection in mice with adjuvant induced arthritis.

In mice and humans two distinct CD4+ helper T cells, known as Th1 and Th2 are identified. They are characterized by the different cytokine milleau they induce. The balance between Th1 and Th2 responses is thought to be decisive for the initiation and course of some autoimmune disorders, as well as for the outcome of infectious processes. In the present study the development of Candida alibcans infection in mice with adjuvant-induced arthritis was investigated. An impaired host resistance against C. alibcans in arthritic mice was registered when the inoculation was done during the early and the established phases of arthritis. In contrast, the slight elevation of the number of survivors was detected when the infection was induced at the peak of inflammation. These data correlated with the changes of serum TNF-alpha level and delayed type hypersensitivity (DTH) to C. alibcans.

Animals↗