Decreased NK cell activity after partial vulvectomy in pregnant patient with vulvar intraepithelial neoplasia 3 (VIN3).

INTRODUCTION AND OBJECTIVE: The study presents the problem of immune disturbances in pregnant women with vulvar carcinoma in situ (VIN3). MATERIAL AND METHODS: NK cell and T reg activity in the study patient were analysed using flow cytometry. RESULTS: Decreased NK cell activity and but increased T reg activity were observed after vulvectomy, with subsequent successful pregnancy outcome. CONCLUSIONS: Although vulvar cancer may influence immune cell activity, this issue merits further study.

Effects of sildenafil citrate and etanercept treatment on TNF-α levels in peripheral blood of women with recurrent miscarriage.

OBJECTIVES: The aim of the study was to determine serum concentrations of a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), in patients with recurrent abortions undergoing treatment with sildenafil or etanercept. MATERIAL AND METHODS: Serum TNF-α concentrations were determined for 24 patients with recurrent miscarriages (aged 32.7 ± 4.64 years) deemed eligible for sildenafil therapy and 7 patients treated with etanercept (aged 37.65 ± 5.45 years). Measurements were performed before and after therapy. The control group included 10 healthy women (aged 33.3 ± 5.49 years), who gave birth at least once without pregnancy-related complications. The levels of serum TNF-α were measured by Elisa. RESULTS: Patients treated with etanercept had significantly elevated levels of TNF-α before therapy as compared to the control group (41.4 ± 28.4 vs. 16.6 ± 7.2 pg/ml). Moreover we found a tendency for the concentration of TNF-α to increase in sera of patients treated with sildenafil after therapy completion (19 ± 29 vs. 15.4 ± 26.7 pg/ml). Treatment with etanercept resulted in a significant reduction of serum TNF-α levels (41.4 ± 28.4 vs. 25.4 ± 3.2 pg/ml). CONCLUSIONS: Therapy of recurrent abortions with anti-TNF-α drugs appears to be encouraging. Administration of blockers of phosphodiesterase type 5 or TNF-α blockers before conception seems to be a promising future therapy of immune-dependent recurrent miscarriages, limiting the teratogenic influence of the drugs on the fetus.

The dysfunction of NK cells in patients with type 2 diabetes and colon cancer.

Glucose metabolism disorders influence anticarcinogenic function of natural killer (NK) cells. The aim of this study was to evaluate the number and cytotoxic activity of NK cells in type 2 diabetic (T2D) patients with negative family history of cancer, type 2 diabetic subjects with newly diagnosed untreated colon cancer (T2DCC) and patients without type 2 diabetes with newly diagnosed, untreated colon cancer (CC). Incubation tests were performed in 18 T2D patients, treated with diet and oral antidiabetic agents, 16 T2DCC; cT1-4N0M0 (c-clinical diagnosis based on computed tomography, colonoscopy and histopathology) treated with diet and oral antidiabetic agents and 16 normoglycemic CC; cT1-4N0M0. Control group included 18 metabolically healthy (with normal fasting glucose and normal glucose tolerance) subjects (HS) with negative family history of cancer, matched by age, BMI and waist circumference. Peripheral blood mononuclear cells were isolated by means of gradient centrifugation. The K562 human erythroleukemia cell line served as the standard target for human NK cytotoxicity assay. The T2D revealed an increased number of NK cells (13.56 ± 5.9 vs 9.50 ± 4.8 %; p < 0.05) when compared with HS, yet these cells had a decreased activity (3.3 ± 2.5 vs 9.4 ± 3.6 %; p < 0.01). The CC demonstrated a decreased activity (2.9 ± 1.8 %; p < 0.01) but a similar number (8.82 ± 3.7 %; not significant) of NK cells when compared to HS. The T2DCC NK cells were characterized by trace cytotoxic activity (1.1 ± 0.7 %; p < 0.01) and nearly three times greater amount (21.24 ± 7.5 %; p < 0.01) when compared to T2D. Type 2 diabetes and CC are associated with disadvantageous alterations of NK cells, leading to impairment in their cytotoxic activity. The impaired activity of NK cells in T2D can be involved in the increased carcinogenic risk and can promote a higher incidence of CC.

Phage as a modulator of immune responses: practical implications for phage therapy.

Although the natural hosts for bacteriophages are bacteria, a growing body of data shows that phages can also interact with some populations of mammalian cells, especially with cells of the immune system. In general, these interactions include two main aspects. The first is the phage immunogenicity, that is, the capacity of phages to induce specific immune responses, in particular the generation of specific antibodies against phage antigens. The other aspect includes the immunomodulatory activity of phages, that is, the nonspecific effects of phages on different functions of major populations of immune cells involved in both innate and adaptive immune responses. These functions include, among others, phagocytosis and the respiratory burst of phagocytic cells, the production of cytokines, and the generation of antibodies against nonphage antigens. The aim of this chapter is to discuss the interactions between phages and cells of the immune system, along with their implications for phage therapy. These topics are presented based on the results of experimental studies and unique data on immunomodulatory effects found in patients with bacterial infections treated with phage preparations.

Etanercept immunotherapy in women with a history of recurrent reproductive failure.

OBJECTIVE: The aim of the study was to evaluate the effect of etanercept immunotherapy on peripheral natural killer (NK) cell activity in women with a history of recurrent miscarriage (RM) or failed in vitro fertilization (IVF). MATERIALS AND METHODS: Thirty nonpregnant women with reproductive failure and increased peripheral NK-cell number and/or activity before conception were studied. Women with reproductive failure received 4 doses (25 mg) of etanercept twice weekly before conception. Peripheral NK-cell activity before and after etanercept therapy in RM women was measured using flow cytometry In addition, the peripheral blood NK-cell surface antigens- CD16- and CD56 and peripheral blood regulatory T cell (T reg) antigens- CD4- and CD25 were studied using flow cytometry before treatment and 2 weeks after the last etanercept dose. RESULTS: NK-cell activity was significantly decreased after etanercept therapy in the study women (P < .05). This effect was significantly higher in women with subsequent pregnancy success (P < .05), but not in those with pregnancy failure (P > .05). There were no significant differences in T reg level before and after etanercept therapy (P > 0.05). CONCLUSION: Etanercept therapy might be effective treatment for women with increased NK-cell activity. Regulation of immune system activity may underlie the possible effect of such therapy.