Oxidative stress has become a major topic; not only is it implicated in many diseases, it may even be one of their causes. Other environmental influences besides UV radiation can also increase oxidative stress on the body, including air pollution, smoking and the consumption of alcohol, and not least infections. Again and again, the talk is of fighting these free (oxygen) radicals by supplementing the diet with the appropriate vitamins.

Researchers at ETH Zurich Institute took these questions as their starting point and have now identified a phenomenon that explains the effects of oxidative stress on immune cells.  The team explain that whenever a foreign body such as a virus or other pathogen enters the human body, a certain class of immune cells, the T cells, jump into action and proliferate rapidly. One sub-class of these cells, the CD8+ T cells, eliminate the virus by killing cells it has infected. Other T cells, known as CD4+ T cells, coordinate the immune response to all kinds of pathogens. These are the generals in the immune system’s army.

But a week can pass before these T cells start to take their toll on a virus, because in the early stages of an infection too few T cells are able to recognise the specific pathogen. Only once they have had contact with the the pathogen do these few scout cells begin to divide and form clones of themselves. With cells dividing every eight to twelve hours, it takes a few days to gather enough cells to overwhelm the infection.

However, this immune response does not work if significant oxidative stress is damaging the T cells and depriving the body of the tools it needs to repair them, as the researchers have now shown in their new study published in the Journal of Experimental Medicine.

The data findings show that if the immune cells lack repair enzyme Gpx4 (or it is defective), the T cells die off as they divide, which means the immune system cannot eliminate the pathogen and the infection becomes chronic. This is the enzyme responsible for repairing oxidative damage to the cell membrane. When testing mice whose immune cells lacked the repair enzyme, the researchers were able to save the immune cells from cell death by mixing a high dose of vitamin E into the animals’ food. That was enough antioxidant to protect the T cells’ cell membranes from damage, so they could multiply and successfully fend off the viral infection. At 500 milligrams per kilogram of mouse feed, this quantity of vitamin E was ten times higher than was present in the standardised normal food.

The researchers demonstrated this by way of a mouse model using animals in which the Gpx4 gene can be deactivated either cell-specifically or at a chosen point in time. The researchers then altered the mouse line so that the Gpx4 gene was inactive only in T cells or certain phagocytes.

The benefit of vitamin tablets is a controversial topic state the team, adding that there is little scientific evidence as yet making a strong case for vitamin supplements.  The group state that their study was all the more interesting because it proved the effectiveness of vitamin E, showing that even a genetic defect in a major part of a cell’s antioxidative machinery can be compensated for by delivering a high dose of vitamin E.

The researchers consider it significant that immune cells suffer the same type of death as certain kinds of cancer cells when treated with a cytostatic drug, and judges this fact to be of scientific value. Known as ferroptosis, this type of programmed cell death was first described in a scientific publication in 2012.  To the team’s knowledge this is the first study to demonstrate that oxidative stress causes immune cells to suffer the same type of death as cancer cells.

The team stress that people with a normal level of health and a balanced diet shouldn’t need vitamin supplements. However, they add that a supplement of vitamin E or other liposoluble antioxidants could well make sense in the event of oxidative stress, which can arise in everyday situations such as an infection or exposure to UV light.

Patients with certain neurodegenerative diseases or diabetes suffer massive oxidative stress, and in these cases antioxidants could be a worthwhile addition to their treatment. The team now plan to move the study onto human trials and work out dosage levels for antioxidants pertaining to the levels of oxidative stress.

Source:  ETH Zurich’s Institute of Molecular Health Sciences