Daily very low UV dose exposure enhances adaptive immunity, compared with a single high-dose exposure. Consequences for the control of a skin infection.

Ultraviolet radiation (UVr) promotes several well-known molecular changes, which may ultimately impact on health. Some of these effects are detrimental, like inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also promotes vitamin D synthesis and other beneficial effects. We recently demonstrated that exposure to very low doses of UVr on four consecutive days [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the recruitment of neutrophils or lymphocytes, as the exposure to a single high UV dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing antimicrobial peptides transcription and epidermal thickness. The aim of this study was to evaluate the adaptive immune response after shUVd and rlUVd, determining T-cell and B-cell responses. Finally, we challenged animals exposed to both irradiation procedures with Staphylococcus aureus to study the overall effects of both innate and adaptive immunity during a cutaneous infection. We observed, as expected, a marked suppression of T-cell and B-cell responses after exposure to an shUVd but a novel and significant increase in both specific responses after exposure to rlUVd. However, the control of the cutaneous S. aureus infection was defective in this last group, suggesting that responses against pathogens cannot be ruled out from isolated stimuli.

HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.

Effect of AC II, a herbal formulation on radiation-induced immunosuppression in mice.

A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.

[Clinical and immunological aspects of low-intensity laser irradiation in patients with gastroduodenal ulcers]. / Kliniko-immunologicheskie aspekty nizkointensivnogo lazernogo izlucheniia u bol'nykh iazvennoi bolezn'iu gastroduodenal'noi zony.

Laser iridotherapy was carried out simultaneously with irradiation of immuno-competent zones on the integument of the human body in patients with stomach and duodenal ulcers. As a result of such treatment, it was discovered that laser therapy has immunomodulating action leading to the reduction of the ulcer cicatrisation period.

[State of humoral immunity and phagocytic activity of neutrophils in patients with ulcer and effect of low-intensity laser therapy]. / Sostoianie gumoral'nogo immuniteta i fagotsitarnoi aktivnosti neitrofilov u bol'nykh iazvennoi bolezn'iu i vliianie na nikh nizkointensivnoi lazernoi terapii.

The aim of our investigation was to study the influence of low-intensity laser therapy at the immunologic parameters and Helicobacter pylori (HP) microbial contamination in patients with exacerbation of peptic and duodenal ulcer. 100 patients aged 18-65 were examined and divided into 2 groups. The experimental group (75 patients) underwent a complex drug and laser therapy of various therapeutic techniques. The control group (25 patients) underwent only drug therapy. The results of this study show the immunocorrective effect of different methods of low-intensity laser therapy in the exacerbation period and more essential decrease of HP microbial contamination in the experimental group.

Ultraviolet light-induced regulatory (suppressor) T cells: an approach for promoting induction of operational allograft tolerance?

Ultraviolet (UV) light is known to induce skin cancers by causing DNA gene mutations and inducing immunosuppression. Taking advantage of these immunosuppressive capacities, UV light has been used, with different modalities, as an immunosuppressive therapy in a variety of diseases including allograft rejection and graft-versus-host disease. Phototherapy includes UVB irradiation, UVA irradiation, oral psoralen (+)UVA irradiation (PUVA), photodynamic therapy, and extracorporeal photopheresis, which consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and incubated with 8-methoxypsoralen. According to numerous experimental models and human data, there is increasing evidence that UVB irradiation and extracorporeal photopheresis can induce regulatory T cells and anticlonotypic activity. These therapies induce apoptosis of activated T cells or of extracorporally treated mononuclear cells, and up-regulate the expression of costimulary molecules and adhesion molecules on antigen presenting cells. UVB- or UVA-induced apoptotic cells could secrete immune suppressive cytokines (interleukin (IL)-4, IL-10). The processing and presentation of apoptotic T cell antigens from clones of pathogenic T cells by activated antigen presenting cells might explain the induction of systemic anticlonotypic activity by photopheresis. This induction of cell-mediated suppressive activity opens up future prospects with the aim of expanding regulatory T cells and/or anticlonotypic activity, especially by photopheresis in organ and cell transplantation.

[The use of laser radiation and sinusoidal modulated currents in the therapy of patients with chronic calculous pyelonephritis]. / Primenenie lazernogo izlucheniia i sinusoidal'nykh modulirovannykh tokov v terapii bol'nykh khronicheskim kal'kuleznym pielonefritom.

The authors present a technique of treating chronic calculous pyelonephritis with laser radiation and sinusoidal modulated currents which promotes a complete elimination of the calculus fragments in 100, 70 and 50% of the patients in the stone size 0.2-0.5 cm, 0.5-0.7 cm and > 7 cm, respectively. This combined therapy had also antiinflammatory, and immunity-stimulating effects.

[The effect of EHF puncture on the immune status of patients with gastric peptic ulcer]. / Vliianie KVCh-punktury na immunnyi status bol'nykh iazvennoi bolen'iu zheludka.

Microwave puncture (MP) effects were compared to effects of 4-component basic medication in 63 patients with gastric ulcer. The study was made of nonspecific defense factors, serum levels of IgA, IgM, IgG, gastric juice levels of IgA, pool structure of circulating lymphocytes (DR+, CD3+, CD22+, CD4+, CD8+), spontaneous and LPS-stimulated Ig-synthetic function of B-lymphocytes. Mean time of the ulcer healing in MP usage made up 14.6 +/- 1.6 days, in standard therapy--27.2 +/- 3.1 days (P < 0.001). Immunomodulating effect shown by MP consisted in activation of nonspecific defense factors and activation of immunoglobulin-synthetizing function of B-lymphocytes.

[Specific antimicrobial immunity in patients with suppurative soft-tissue diseases undergoing conventional and modified ultraviolet irradiation of autologous blood]. / Spetsificheskii antimikrobnyi immunitet u bol'nykh s gnoinymi zabolevaniiami miagkikh tkanei pri obychnom i modifitsirovannom ul'trafioletovom obluchenii autokrovi.

Study of titers of specific antibacterial antibodies in the plasma by passive hemagglutination test and of the number of antibody-producing cells (APC) by local hemolysis test in patients with purulent diseases of soft tissues showed that both values increased after UV exposure of autoblood. This increase was more expressed after differentiated exposure of erythrocytic and leukocytic mass than after common UV exposure, which is explained by more complete exposure of leukocytes participating in immunological reactions. Study of APC during a UV session showed an increase in the count of these cells 6-8 h after exposure.

Biological effects of narrow-band (311 nm TL01) UVB irradiation: a review.

The narrow-band UVB (TL01) lamp (311 nm emission) was developed for use in phototherapy, as an alternative to a broad-band UVB source and to photochemotherapy, both of which have significant side effects and carry a risk of carcinogenesis. This new lamp has proved to be particularly effective at clearing psoriasis. It is now acknowledged that the TL01 lamp is probably 2-3 times more carcinogenic per minimum erythema dose than broad-band UVB, but the cumulative dose required in therapy is considerably less than when using broad-band UVB sources. In terms of irradiation dose, the TL01 lamp is about 5-10-fold less potent than broad-band UVB for erythema induction, hyperplasia, oedema, sunburn cell formation and Langerhans cell depletion from skin. However, the broad-band UVB to TL01 potency ratio for cis-urocanic acid formation in the skin is approximately unity. In addition, the TL01 lamp, as used in phototherapy, has relatively more suppressive effects than broad-band UVB on systemic immune responses as judged by natural killer cell activity, lymphoproliferation and cytokine responses. However, the TL01 lamp is less effective at reducing epidermal antigen presentation, inducing dendritic cell migration to lymph nodes draining irradiated sites and suppressing contact hypersensitivity at the doses tested. Therefore the use of the TL01 lamp in phototherapy should be considered carefully after weighing up its diverse effects on the skin and immune system.

Effect of selenium in recovery of immunity damaged by H2O2 and 60Co radiation.

Con A stimulated lymphocytes proliferation was measured as [3H]thymidine incorporation and IgG was quantified by single radial immunodiffusion to study recovering or protecting effect of selenium (Se) on immunity attacked by exogenous active oxygen species, H2O2 and 60Co-radiation, respectively. Lipid peroxidation was also determined to observe the relation between antioxidation ability and protecting ability of Se. It was found that H2O2 injured lymphocytes immunocompetence deeply and 60Co-radiation decreased immune response capacity greatly, but that administration of Se counteracts this damage. The antioxidative ability of Se was correlated with its protecting ability.

[Characteristics of the humoral immune system and lipid peroxidation processes in people living in territories contaminated with radionuclides]. / Kharakteristika sistemy gumoral'nogo immuniteta i protsessov perekisnogo okisleniia lipidov u lits, prozhivaiushchikh na territoriakh, zagriaznennykh radionuklidami.

Among 33 patients with Stage II hypertension, 25 persons were inhabitants of the Russian radionuclide-contaminated areas and 8 patients had no prior contacts with ionizing radiation (control). All the patients examined were maintained within 4 weeks on a diet, radioprotective effect of which was realized due to the elevated content of sulfur containing amino acids, antioxidants and complexes. In the patients who lived in the radionuclide-contaminated areas, a moderate activation of lipid peroxidation was detected simultaneously with marked alterations in the humoral component of the immunity system, which involved a considerable increase in the levels of IgG and complements C3 and C4. A decrease in content of malonic dialdehyde and diene conjugates as well as normalization of IgG and decrease in content of IgA, IgM and C3 were observed in blood plasma of the patients on diet. Supplementation of omega 3 polyunsaturated fatty acids (omega 3-PUFA), 5 g/day and alpha-tocopherol, 12.5 mg/day, to the diet elevated the serum concentrations of all lg classes, which suggests the presence of an immunomodulating effect of omega 3-PUFA. Moreover, the content of malonic dialdehyde was not increased in blood plasma if 3-PUFA was used. Hence, increased alpha-tocopherol levels should be used in the treatment of these patients with omega 3-PUFA (up to 5-7 mg per g PUFA) in order to stabilize lipid peroxidation.

[The effect of quantum hemotherapy on cellular and humoral immunity and on erythrocyte morphology in patients with ischemic heart disease]. / Vliianie kvantovoi gemoterapii na sostoianie kletochnogo i gumoral'nogo immuniteta i morfologiiu éritrotsitov u bol'nykh ishemicheskoi bolezn'iu serdtsa.

A study is presented of the effect of reinfusions of ultraviolet-irradiated autologous blood on the number of lymphocytes, titer of circulating immune complexes and theophylline-sensitive cells, number of immunoglobulins A, G and M, number and form of erythrocytes in 30 patients with stable and progressive exertion stenocardia. Thirty control patients were treated with nitrates, calcium antagonists and acetylsalicylic acid. It was established that in patients with stenocardia quantum hemotherapy produces an immunocorrective action reduces the titer of circulating immune complexes, the content of T-lymphocytes, the number of immunoglobulins A and G, normalizes the morphological and functional activity of erythrocytes. Use of this method in the treatment of ischemic heart disease is pathogenetically justified and prevents development of myocardial infarction.

[Immune shifts in patients with thyrotoxicosis under the effect of the autotransfusion of UV-irradiated blood]. / Immunnye sdvigi u bol'nykh tireotoksikozom pod vliianiem AUFOK.

The authors have carried on an investigation of humoral immunity in 64 patients with thyrotoxicosis of different degrees. It was found that patients with different degrees of thyrotoxicosis had an elevated level of immunoglobulins and that autotransfusion of UV irradiated blood considerably normalized the content of immunoglobulins in blood serum, especially in patients with mild and mean degrees of thyrotoxicosis.

Investigation of immunoglobulin (IgG, IgA, IgM) levels in the blood serum of uranium miners after higher and lower exposure to ionizing radiation.

The levels of IgG, IgA and IgM were measured in the blood serum of uranium miners in a minin-district, where after a geological disturbance exposure to a high level of ionizing radiation took place. The mean exposure to 222-Rn daughters after first year was 7.35 WLM, after the second year 0.13 WLM only. Serum was sampled before miners started their occupation, for the second time after the first year and for the third time after the second year. The levels of IgG and IgM significantly decreased after one year of exposure, while the IgA changed only slightly. After the second year the levels of IgG and IgM significantly rose. IgG exceeded the initial levels: a regenerative hypercompensation took place. On the other hand IgA at the same time decreased. The IgG levels are only slightly correlated with radiation dose rate; for IgA and IgM the correlation is lacking. Individual Ig levels appear to be very variable. The reduction of IgG reached hypogammaglobulinemic levels in some miners after the first year and was followed by a propensity to infections of the respiratory tract. The significance of these observations is discussed from the immunological, radiological and radiohygienical point of view.