Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127−FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

INCREASE IN NKT CELLS – A MARKER OF EARLY PROGRESSING AT ADJUVANTVACCINOTHERAPY OF PATIENTS WITH A METASTATIC MELANOMA OF SKIN

Introduction. Natural killer T lymphocytes (NKT) take place between the innate and acquired immune response. The ability of these cells to activate the antitumor immune response and inhibit immunological activity makes them the target of research in cancer patients. The radicality of surgical treatment of patients with metastatic melanoma (stage III–IV) is relatively conventional. In this regard, the possibility of adjuvant effective therapy of melanoma is actively investigated worldwide.The aim of the study is investigation of the importance of increasing the number of NKT cells in the peripheral blood of patients with metastatic melanoma after radical surgical removal of the tumor. Patients were treated with adjuvant regimen antitumor autologous dendritic cell therapy in form of vaccination.Materials and methods. The study included 39 patients with stage III and IV metastatic melanoma with regional and / or distant metastases after radical surgery. From the peripheral blood monocytes of each patient, an autologous vaccine was created from mature dendritic cells loaded with tumor lysate. The therapy continued until objective progression. The study included patients who received from 5 to 120 injections. The follow-up period ranged from 5 to 168 months.Results. It was shown that 14 (36 %) of patients had the number of NKT cells exceeding the norm (0–10 %) and in the course of vaccine therapy they had the progression of the disease in the period up to 2 years. In patients with relapse-free course of the disease in vaccine therapy (n = 13), the number of NKT lymphocytes did not exceed the norm both before and during therapy. Significantly shorter time to progression was revealed in patients with high initial content of NKT lymphocytes compared with patients with normal indices of NKT cells (6.5 months) – 95 % confidence limit 2,4–10,7 % vs 96,2 months (95 % confidence limit 63.8–128.6 %). Conclusion. An increased number of NKT cells in patients with stage III–IV metastatic melanoma after radical surgical treatment is a marker of early progression.

PARP2 deficiency affects invariant-NKT-cell maturation and protects mice from concanavalin A-induced liver injury

Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2−/− mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis. NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice.

Influenza Virus Infection but Not H1N1 Influenza Virus Immunization Is Associated with Changes in Peripheral Blood NK Cell Subset Levels

ABSTRACTThe innate immune system constitutes the first line of defense against viral agents, and NK cells seem to have an important protective role during the early phases of influenza virus infections. We decided to assess the levels of NK and NKT lymphocytes and the expression levels of different membrane receptors (NKp44, NKp46, NKG2A, killer cell immune-like receptor [KIR] 3DL1/DS1, KIR2DL1/DS1, and CD161) in peripheral blood samples of patients with influenza (n= 17) and healthy individuals immunized against this virus (seasonal and [H1N1]pdm2009 influenza vaccines;n= 15 and 12, respectively). Blood samples were obtained from all individuals, and NK and NKT cell subsets were analyzed by multiparametric flow cytometry. We found that the patients with severe influenza (n= 9) showed significant increases in the percentages of NKp46+NKp44+NK cells and the proportions of NK and NKT lymphocytes expressing KIR2DL1 and KIR3DL1 and reductions in the percentages of NKp46+NKp44−NK cells compared to those in the healthy controls (n= 27). In contrast, influenza immunization, against either the seasonal or the pandemic H1N1 virus, was not associated with important changes in the levels of NK and NKT lymphocytes or the expression levels of the different receptors by these cells. Our data suggest that severe influenza is associated with important and complex alterations on NK cells, which might contribute to the pathogenesis of this condition.

Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-κB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-γ levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.