bacteria Promising. "In several animal models, selenium status was reported to affect the immune response after bacterial infections. Combined pretreatment with selenium and the antibiotic ciprofloxacin for 4 wk was more effective than ciprofloxacin alone to prevent the development of chronic bacterial prostatitis in rats after infusion of an Escherichia coli suspension into the prostatic urethra (90). Compared with mice fed an adequate-selenium diet, selenium-deficient mice showed a compromised response of the innate immune system after infection with the gram-positive bacterium Listeria monocytogenes (91). The innate as well as the humoral immune response was impaired in selenium-deficient sheep affected by foot root, an endemic disease of ruminants caused by infection of claws with the gram-negative bacterium Dichelobacter nodosus. Selenium supplementation did not prevent footrot but restored immune functions (92). In dairy cows, selenium deficiency has been associated with increased incidence and severity of intramammary infections by E. coli and Staphylococcus aureus; combined supplementation with selenium and vitamin E improved the intracellular bacterial killing in blood neutrophils." cancer Upregulates IL-2, the first effective immunotherapy in human cancer "Similar doses of selenium were found to be effective both in infectious diseases and in cancer prevention. This is intriguing and deserves closer attention to the mechanistic links, because cancer and infectious diseases share similarities such as the involvement of ROS/RNS synthase, the host T cell response, and the activation of common signaling pathways that mediate and amplify inflammation (94). Supranutritional selenium increases the production of the proinflammatory cytokine IL-2 in CD4+ T cells activated by T cell receptor stimulation (7, 21, 22), and interestingly, IL-2 was used as the first effective immunotherapy in human cancer (95)." "An earlier intervention trial in Linxian County, China, reported a significant decrease in gastric cancer mortality among participants supplemented for 5 y with a mixture of selenium, vitamin E, and β-carotene compared with the placebo group." cox Keshan Disease "Keshan disease, an endemic cardiomyopathy named after an outbreak in the Keshan County, China, in 1935, used to occur in areas of China with very low selenium content in the soil." "Infection with a noncardiovirulent strain of Coxsackie B virus (CVB3/0) caused heart damage similar to human pathology only in selenium-deficient mice, whereas mice fed a selenium-adequate diet (0.2 ppm Se as selenite) were protected. The selenium-deficient mice exhibited higher virus titers in the heart and decreased antigen-specific T cell responses than their selenium-adequate littermates (35). In selenium-deficient mice, the formerly benign CVB3/0 strain mutated to a pathogenic geno- and phenotype; 4 out of the 6 specific nucleotide exchanges in the viral RNA were located in the coding region of proteins and resulted in amino acid exchanges" "An insufficient supply of selenium and other micronutrients was also hypothesized to be linked to the emergence of an epidemic neuropathy in Cuba in the early 1990s." The coxsackievirus infection is made worse because selenium deficiency weakens the host's immunity, preventing the virus from being effectively challenged by T-cell lymphocytes or antibodies. As a result, the mutated virus can reproduce faster than it would in a relatively healthy person. In addition, the lack of selenium prevents the quenching of mutation-causing free radicals, so when the virus reproduces, it also mutates at a faster rate. Although Beck and Levander studied only one virus, the implications are profound. They have already begun looking at whether other "host" nutritional deficiencies cause viral mutations as well. According to Beck, this propensity to mutate in a selenium-deficient animal or person might explain why new influenza strains regularly emerge from China, where selenium deficient soils are common. The flu virus originates in Chinese ducks, jumps to pigs, and then infects people." ebola The source of innate Baka immunity. "Dietary supplementation with selenium-containing multimicronutrients might also be useful to improve supportive care and to strengthen the immune system of patients suffering from newly emerging viral diseases, such as in the current epidemic of Ebola fever in West Africa. Populations in several countries most afflicted by past and current outbreaks of Ebola fever (e.g., Liberia, Guinea, Democratic Republic of Congo) exhibit a high risk of selenium deficiency, and strikingly, the lowest dietary selenium supply in Africa was reported from Liberia, with a daily intake of only 23 μg Se.". Note: Zaire/Congo is lower and it's been shown up to 33% of Baka ("pygmy") villages in Gabon have a natural immunity to the Ebola Zaire virus. IRD did the assay, the New York times covered the story in 2010. hcv Hepatitis C Virus "Plasma selenium concentrations and GPx activity as well as selenium concentrations in erythrocytes were significantly lower in HCV-infected patients than in healthy controls, and selenium concentrations in both plasma and erythrocytes of patients were inversely correlated with HCV virus load (62). Moreover, HCV/HIV-coinfected patients had lower serum selenium concentrations than did HIV-infected patients without concomitant HCV infection (51). In a small intervention trial, Danish HCV-infected patients were supplemented for 6 mo with vitamins C and E together with 200 μg Se/d as selenomethionine. However, no beneficial effect with respect to viral load and liver damage was observed in the micronutrient group." hiv HIV/AIDS Human HIV-1 and HIV-2 retroviruses are enveloped, single-stranded RNA viruses. Untreated HIV infection causes progressive failure of the immune system, resulting in AIDS. Antiretroviral therapy (ART) with a combined drug consisting of a protease inhibitor and 2 reverse transcriptase inhibitors has made HIV infection a manageable chronic disease. Despite this progress, ART is expensive, does not fully restore the immune system, and has considerable side effects (48). Deficiencies in micronutrients, including selenium, are widespread in HIV-infected individuals, most notably under resource-limited conditions, and their remedy can be a reliable, beneficial, and safe measure to support ART." HIV-infected adults from Botswana with a CD4+ T cell count >350/μL were supplemented for 2 y with either 200 μg Se/d, a vitamin mixture (B-vitamins, vitamins C and E) or vitamins plus selenium. Neither the vitamins nor selenium alone affected any of the clinical variables, whereas the combination of selenium and vitamins significantly lowered disease progression as measured by decline in CD4+ T cells and morbidity (58). Even though the data are still inconsistent and insufficient, there is some evidence that selenium supplementation may delay the progressive destruction of CD4+ T cells and the onset of AIDS and decrease the risk of comorbidities. This approach is particularly promising when selenium is given in combination with other micronutrients. Although there is currently no evidence for an influence of the host selenium status on the mutation rate of HIV, the selenoenzyme TrxR1 has been identified as a negative regulator of the HIV-encoded Tat protein that is required for virus replication. iav Avian Influenza "When transgenic mice with impaired biosynthesis of selenoproteins were infected with the mild influenza A/Bangkok/1/79 virus strain, they showed delayed virus clearance but a similar severity of the lung pathology compared with wild-type mice with normal selenoprotein expression. The GPx activity in lungs of the transgenic mice was 82% lower than in selenium-adequate wild-type mice but slightly (12.5%) higher than in wild-type selenium-deficient mice, suggesting a threshold level of GPx activity required for antiviral protection (44)." "The impact of selenium on the outcome of the immune response appears to depend on the virulence of the applied IAV strain as well. Infection with influenza A/NWS/33 (H1N1) virus resulted in high (75%) mortality in selenium-deficient mice, whereas selenium supplementation up to 0.5 ppm (as selenite) dose-dependently lowered the mortality rate, accompanied by increased production of the Th1 cytokines IFN-γ and TNF-α (45). Another study that used an IAV strain that is highly pathogenic in mice yielded opposing results: 50% of the mice in the selenium-adequate group died 7 d postinfection with influenza A/Puerto Rico/8/34 virus, whereas there were no deaths in the selenium-deficient group. Virus-induced induction of Th1 cytokines did not differ between the 2 groups, but the selenium-deficient mice exhibited less pronounced induction of Th1-related chemokines and strong induction of the Th2 cytokine IL-4 (46)." "Thus, the shift toward Th2 immunity under selenium-deficient conditions appears to limit or delay the host immune response. This may result either in a beneficial outcome with better recovery from infection with a highly virulent IAV strain due to less immunopathology or in an adverse outcome with immune escape and mutation of less virulent to more virulent pathogens. On the other hand, optimized expression/activity of GPx under selenium-adequate conditions may protect infected cells and tissues from IAV-induced oxidative damage and cell death. Cultured selenium-deficient differentiated bronchial epithelial cells showed more apoptotic cell death upon infection with IAV than did cells grown in selenium-adequate medium"

polio Polio viruses "Poliovirus is a nonenveloped, single-stranded RNA virus. An intervention trial in healthy British adults with a modest selenium deficit [plasma Se <94 μg/L (1.2 μM)] investigated the effect of selenium supplementation on the immune reaction against a live attenuated poliovirus vaccine (64). Before vaccination, participants received 50 or 100 μg Se/d as selenite or a placebo for 15 wk. Poliovirus-induced lymphocyte proliferation as well as production of the Th1 cytokine IFN-γ and the Th2 cytokine IL-10 occurred faster in both selenium-supplemented groups than in the placebo group. Participants supplemented with 100 μg Se/d showed a significantly higher number of total T cells and Th cells after the virus challenge and a better virus clearance. Moreover, the mutation rate of the poliovirus was lowered in the selenium-supplemented subjects. Selenium supplementation augmented and accelerated the cellular antiviral immune response, but it did not shift the Th1/Th2 balance and it did not affect the humoral response" pylori Helicobacter pylori "It has been estimated that this gram-negative, helix-shaped bacterium colonizes the upper gastrointestinal tract of >50% of the human population worldwide. Nontreated Helicobacter pylori infection is a major pathogenic factor for the development of gastritis, gastric cancer, and duodenal ulcer (83, 84). Micronutrient homeostasis is frequently impaired in H. pylori–infected individuals, probably through malabsorption, lowered gastric acid secretion, and atrophy of the gastric mucosa (85). A recent meta-analysis of epidemiologic data from 46 studies on vitamins and 10 studies on trace elements identified a significant association of H. pylori infection with lowered concentrations of ascorbic acid and cobalamin, whereas there was not enough evidence for trace elements including selenium because of the limited number of studies." rnav RNA viruses "Dietary selenium supplementation of human populations at risk of modest selenium deficiency—as in many countries in Europe and Africa and some regions in East Asia—might serve as an inexpensive and widely available adjuvant therapy of viral infections. Intriguingly, beneficial effects of selenium have almost exclusively been reported for infections by RNA viruses, whereas information on selenium and DNA viruses remains scarce. A noteworthy exception is provided by an intervention trial in the Chinese Qidong province, a region with selenium-poor soil: selenium supplementation lowered the incidence of liver cancer associated with infection by hepatitis B virus, a DNA virus." tb Tuburculosis Currently available data do not offer sufficient clues to judge whether individuals with or without HIV coinfection might benefit more. {Note: so much of the work with TB is heavily dependent on observations of HIV patients. Looking at broken immune systems to learn how heatlthy ones should behave is pointless. There is evidenc selenium drops in TB. - RJS) wnv West Nile Virus Selenium status and the impact of dietary selenium supplementation in WNV-infected humans have not been investigated yet, but there is in vitro and in vivo evidence for a beneficial role of selenium. Selenium-deficient monkey kidney epithelial cells were more prone to virus-induced apoptotic cell death than cells cultured in selenium-supplemented (50 nM selenite) medium (66). The selenium-inducible selenoprotein K (SelK), a selenoprotein that is relatively highly expressed in immune cells and located in the endoplasmic reticulum, appears to be involved in the protective action of selenium (67). Mice with targeted deletion of SelK exhibited decreased viral clearance in the periphery and elevated viral titers in the brain upon WNV infection. all Full paper. Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions.