Ultraviolet radiation, vitamin D, and COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become pandemic on March 11th, 2020. COVID-19 has a range of symptoms that includes fever, fatigue, dry cough, aches, and labored breathing to acute respiratory distress and possibly death. Health systems and hospitals have been completely rearranged since March 2020 in order to limit the high rate of virus spreading. Hence, a great debate on deferrable visits and treatments including phototherapy for skin diseases is developing. In particular, as regards phototherapy very few data are currently available regarding the chance to continue it, even if it may be a useful resource for treating numerous dermatological patients. However, phototherapy has an immunosuppressive action possibly facilitating virus infection. In the context of COVID-19 infection risk it is important to pointed out whether sunlight, phototherapy and in particular ultraviolet radiation (UV-R) constitute or not a risk for patients. In this review we aimed to focus on the relationship between UV-R, sunlight, phototherapy, and viral infections particularly focusing on COVID-19.

KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 µg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.

Rat tissue reaction and cytokine production induced by antimicrobial photodynamic therapy.

BACKGROUND: The antimicrobial photodynamic therapy (aPDT) inactivates the target cell via reactions among the photosensitizer (PS), Laser or Led and O2. The aim of this study was to evaluate the tissue reaction and cytokine production promoted by aPDT with curcumin photosensitizer. METHODS: Polyethylene tubes containing saline solution (control), 5% sodium hypochlorite (NaOCl) and aPDT with curcumin PS 500mg/L, were implanted into dorsal connective tissue of Wistar rats. After 7, 15, 30, 60 and 90days of implantation, the animals were euthanized and the tubes with surrounding tissues were removed. The specimens were divided in two part, one half was processed, fixed and prepared for histological analysis by staining with hematoxylin and eosin. The other half was collected for IL-1ß and IL-6 cytokine production using ELISA assay. The results were statistically analyzed by Kruskal-Wallis test followed by Dunn test (p<0.05) for tissue reaction and ANOVA followed by Bonferroni's correction (p<0.05) for ELISA. RESULTS: All groups showed severe tissue reactions at 7days, whilst a significantly decrease by time was observed. Regarding to cytokine production, aPDT increases the IL-1ß levels in all periods of time (p<0.05). However, for IL-6 levels, the highest value was observed with aPDT on the 90th day (p<0.05). CONCLUSIONS: aPDT with curcumin PS 500mg/L demonstrated biocompatibility similar to saline solution and induced the IL-1ß and IL-6 cytokines production.

The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease.

The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections. We conducted a thorough comparison of the molecular and cellular mechanisms of action of UVR and vitamin D on pathogen fitness and host immunity and related these to the effects observed in animal models and clinical trials to understand their independent and complementary effects on infectious disease outcome. UVR and vitamin D share common pathways of innate immune activation primarily via antimicrobial peptide production, and adaptive immune suppression. Whilst UVR can induce vitamin D-independent effects in the skin, such as the generation of photoproducts activating interferon signaling, vitamin D has a larger systemic effect due to its autocrine and paracrine modulation of cellular responses in a range of tissues. However, the seasonal patterns in infectious disease prevalence are not solely driven by variation in UVR and vitamin D levels across latitudes. Vector-borne pathogens show a strong seasonality of infection correlated to climatic conditions favoring their replication. Conversely, pathogens, such as influenza A virus, Mycobacterium tuberculosis and human immunodeficiency virus type 1, have strong evidence to support their interaction with vitamin D. Thus, UVR has both vitamin D-dependent and independent effects on infectious diseases; these effects vary depending on the pathogen of interest and the effects can be complementary or antagonistic.

The role of UVR and vitamin D on T cells and inflammatory bowel disease.

Vitamin D deficiency is associated with the development of inflammatory bowel disease (IBD). In experimental IBD the targets of vitamin D that result in protection from IBD include gut epithelial cells, innate immune cells, T cells, and the microbiota. Ultraviolet radiation (UVR) induces production of vitamin D in the skin and suppresses T cell responses in the host. There is limited data demonstrating an effect of UVR on experimental IBD but the mechanisms of UVR suppression in IBD have not been defined. There are several shared effects of vitamin D and UVR on T cells including inhibition of proliferation and suppression of IFN-γ and IL-17 producing T cells. Conversely UVR decreases and vitamin D increases IL-4 production from T cells. Together the data suggest that UVR suppression of T cells and potentially IBD are both vitamin D dependent and independent.

The symbiosis of phototherapy and photoimmunology.

The health benefits of natural sunlight have been noted since the rise of civilization, even without the knowledge of its mechanisms of action. Currently, phototherapy remains an effective and widely used treatment for a variety of skin diseases. Ultraviolet radiation, from either the sun or artificial light sources, has a profound immunomodulatory effect that is responsible for its beneficial clinical outcomes. Ultraviolet radiation mostly induces the innate while suppressing the adaptive immune system, leading to both local and systemic effects. It is antigen specific, acts on both effector and regulatory T cells, alters antigen-presenting cell function, and induces the secretion of cytokines and soluble mediators. This review provides an overview of the immunologic mechanisms by which ultraviolet radiation is responsible for the therapeutic effects of phototherapy.

[Effect of prolonged administration of low doses of essential oils on the immune response and sensitivity of mice to the action of ionizing radiation].

The effect of ionizing radiation (1 Gy) on the immunological characteristics of spleen in the mice that consumed essential oils of oregano, clove bud and the mixture of lemon oil with ginger extract at low doses with drinking water for 6 months was studied. It was found that the essential oils increased the content of antibody forming lymphocyte cells in the spleen. The maximal effect in comparison with control was found for essential oil of clove bud.

Immunological response induced by alternated cooling and heating of breast tumor.

A new in-situ thermal physical method combining both cryosurgery and local hyperthermia was used to treat mice bearing 4T1 murine mammary carcinoma. The induced anti-tumor immune response was investigated. The cryo/heat treatment resulted in stimulation of CTL response and attraction of immunocytes into the tumor debris, which correlated well to the tumor rejection in re-implantation. The results suggested that alternated cooling and heating had synergistic effect and might be developed into an alternative modality for tumor therapy.

[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.

[Effect of various physical factors on clinical and laboratory indicators and on nonspecific resistance of the body in reactive arthritis]. / Vliianie nekotorykh fizicheskikh faktorov na kliniko-laboratornye pokazateli i nespetsificheskuiu rezistentnost' organizma pri reaktivnykh artritakh.

Application of UV-therapy and acupuncture in the complex therapy and rehabilitation of reactive arthritis patients had a positive effect on the disease course. The clinical efficacy of the compared physiotherapy methodologies is determined, to a certain degree, by the increase in the nonspecific resistance of the organism in this category of patients.

[Use of ultraviolet irradiation of the blood in the complex treatment of peritonitis]. / Primenenie ul'trafioletovogo oblucheniia krovi v kompleksnom lechenii peritonita.

According to the data of tetrasolium nitroblue test and titer of the blood serum antibodies to the most frequently cultured microflora in complex treatment of 27 patients with diffuse purulent peritonitis, it was established, that the use of ultraviolet irradiation of the blood stimulated the specific and non-specific organism resistance.

[Nonspecific resistance during preoperative chemoradiation treatment and UHF hyperthermia of osteogenic sarcoma]. / Nespestsificheskaia rezistentnost' pri predoperatsionnom khimioluchevom lechenii i UVCh-gipertermii osteogennoi sarkomy.

The extent of metastatic spread and the life span depend on the level of nonspecific resistance of the body of patients with osteogenic sarcoma. Chemoradiation therapy reduces antitumoral resistance of patients, and the use of local UHF hyperthermia prevents this negative effect of complex treatment.

Characteristics of mononuclear phagocytes mediating antilisterial resistance in splenectomized mice.

The characteristics of mononuclear phagocytes mediating resistance to infection with Listeria monocytogenes during the early phase (up to 48 h) of the response were investigated in mice of the A strain that had undergone splenectomy. Although irradiation in the sham-operated host had no effect on its antilisterial response when administered immediately before infection, it markedly reduced the ability of the splenectomized host to resist listerial challenge. This effect of radiation was demonstrable in the high-dose range (600 r) and could not be reversed immediately by repopulation with 20 x 10(6) syngeneic nucleated bone marrow cells. Administration of silica 24 h before infection profoundly enhanced the growth of L. monocytogenes in the liver of splenectomized mice. Shielding of the liver, but not the bone marrow, protected the splenectomized host against the effects of radiation, indicating that the cell population responsible for mediating the enhanced antilisterial resistance resides in the liver. The enhanced antilisterial resistance of splenectomized mice was specifically because of the absence of the spleen and not merely because of the removal of a favorable replicating environment for listeria organisms.

Stimulation of resistance against local tumor growth, of hosts pretreated by combined local hyperthermia and X-irradiation.

The relationships involved in host resistance to tumor development were studied. Animals were pretreated by local hyperthermia, local irradiation and combined local hyperthermia and x-irradiation. After treatment, the animals were inoculated with tumor cells 0--96 or 0--120 hours post treatment. (BALB/c X C57B1/6)F1 mice were inoculated with the SV40 local fibrosarcoma, and (C3H/eB/B1)F1 mice were inoculated with the metastatic Lewis lung carcinoma. The results show an enhanced resistance to tumor development in animals pretreated by the combined simultaneous local heat and x-irradiation, as compared to animals only preirradiated, only preheated, or to control untreated tumor-bearing animals.