Study finds seasons may affect immune system activity

"Winter immune boost may actually cause deaths," The Guardian reports. A new gene study suggests there may be an increase in inflammation levels during winter, which can protect against infection but could also make the body more vulnerable to other chronic diseases.

The study looked at gene expression (the process of using a gene to make a protein) in blood samples taken from 1,315 children and adults in different months throughout the year in a range of different countries. The researchers found increased activity of some of the genes involved in inflammation during the winter, and decreased activity in the summer.

The authors concluded that this seasonal change in the immune system could, for example, contribute to the worsening of some autoimmune disorders during the winter, such as rheumatoid arthritis.

But the immune system is extremely complex, and different genes showed different seasonal expression patterns. There were also important discrepancies in expression patterns in different parts of the world. Saying the immune system is "weaker" in certain seasons at this stage is therefore oversimplifying the findings of this research.

It is also likely these seasonal changes could at least in part be a response to changes in infections and allergens, such as pollen in the summer, but this type of study cannot prove cause and effect. Further research into this area is required before any practical application of these results can be found. 

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and the London School of Hygiene and Tropical Medicine in the UK, and the Technical University of Munich and the Technical University of Dresden in Germany.

It was funded by various institutions, including the National Institute for Health Research, Cambridge Biomedical Research Centre, the UK Medical Research Council (MRC), The Wellcome Trust, and the UK Department for International Development.

The study was published in the peer-reviewed journal Nature Communications. This is an open-access journal, so the study is free to read online.

The media, on the whole, reported the story accurately, though the total number of people who had gene expression analyses was 1,315, not more than 16,000, as reported.

Many of the news sources talked of the immune system being "stronger", "weaker" or "boosted". These terms are, arguably, overly simplistic and not representative of the findings of this research. It is probably better to think of the overall pattern of immune activity changing from season to season, rather than the immune system going from "weak" to "strong", and back to "weak" again.

The Mail Online also reported that it is believed the amount of daylight we get "plays a role" in this increased immune activity. They say this "could explain why the seasonal effect was weaker in people from Iceland, where the extremely long summer days and short, dark winter days may upset the process". But this seems contradictory – if daylight plays a role, you would expect a greater seasonal effect in Iceland. 

What kind of research was this?

This research combined several observational studies that looked at the level of immune system activity at different times of the year in people from around the world.

It aimed to see if there was seasonal variation in the:

• gene expression of inflammatory proteins and receptors such as interleukin-6 (IL-6) and C-reactive protein (these proteins are associated with autoimmune conditions such as rheumatoid arthritis)
• number of each type of white cell in the blood (white cells fight different types of infections)

As these were observational studies, they can only show an association between the different seasons and the immune system. They cannot prove that the season causes the immune system to become more or less active, as there could be other factors (confounders) causing any results seen.

What did the research involve?

The researchers looked at the gene expression of nearly 23,000 genes in one type of white blood cell in samples of blood taken from children and adults at different times of the year.

They measured the number of each type of white cell in blood samples from healthy adults from the UK and The Gambia taken during different months. They then looked at gene expression in samples of fat tissue from women in the UK.

Gene expression of 22,822 genes was analysed in samples from 109 children genetically at risk of developing type 1 diabetes. The samples came from the German BABYDIET study, where babies had a blood test taken every three months until the age of three.

Gene expression was measured from blood samples taken at different times of the year from:

• 236 adults with type 1 diabetes from the UK
• adults with asthma but no reported current infection from Australia (26 people), the UK/Ireland (26 people), the US (37 people) and Iceland (29 people)

The researchers then measured the number of each type of white cell in blood samples taken from 7,343 healthy adults from the UK and 4,200 healthy children and adults from The Gambia. They wanted to see if there were seasonal changes in the types of white cells in the blood.

Finally, they looked at gene expression in fat tissue samples taken from 856 women from the UK. They did this to see whether only cells in the immune system showed variation in gene expression with the seasons. 

What were the basic results?

In the first group of children and adults from Germany, the researchers found almost a quarter of all genes (23%, about 5,000 genes) showed seasonal variation in the white blood cells assessed. Some genes were more active in the summer and others in winter.

When looking at all of the population groups they tested, 147 genes were found to show the same seasonal variation in the blood samples taken from the children and adults from the UK/Ireland, Australia and the US.

Again, some genes were more active in the summer and others in the winter. The genes included one encoding protein, which controls the production of anti-inflammatory proteins and was found to be more active in the summer months.

Other genes involved in promoting inflammation were more active in the winter. Seasonal genes from the samples of Icelandic people did not show the same pattern.

The numbers of different types of white blood cells from the UK samples also showed seasonal variation. Lymphocytes, which mostly fight viral infections, were highest in October and lowest in March. Eosinophils, which have many immune functions, including allergic reactions, were highest in the summer.

There were also seasonal patterns in the numbers of different types of white blood cell from people in The Gambia, but these were different from those in the UK. All white cell types increased during the rainy season.

The researchers also found some genes showed seasonal variation in their activity in fat cells.  

How did the researchers interpret the results?

The researchers say their results indicate gene expression and the composition of blood varies with seasons and geographical locations.

They say the increased gene expression of inflammatory proteins in the European winter may help explain why some autoimmune conditions are more likely to start in the winter, such as type 1 diabetes.

Conclusion

This research found seasonal variations in gene expression in one type of white blood cell. Some genes became more active in the summer months, while others became more active in the winter.

For example, one gene involved in the body's anti-inflammation response was increased during the summer, while some involved in inflammation were increased in the winter.

The researchers also found seasonal variation in the numbers of each type of white cell. These patterns were different in samples taken from people in the UK, compared with people from The Gambia.

Because of the observational nature of each study, it is not possible to say for certain that the time of year caused the results seen. The immune system is affected by a variety of factors, such as current and past infections, stress and exposure to allergens.

For example, it is not surprising that the number of eosinophils was highest in the UK during the summer months, when the allergen pollen (linked to hay fever) is most abundant.

Concurrent illness may have confounded the results of the gene expression studies, as they were performed on adults with either type 1 diabetes or asthma and children at increased risk of type 1 diabetes.

The immune system is extremely intricate, involving a wide range of different genes, proteins and cells that have complex interactions, as shown in this study. Further research into this area is required before any practical application of these results can be found.

The most season-specific health advice we can offer at this point is to wrap up warm in winter, avoid getting sunburnt during the summer, and take the opportunity to safely top up your vitamin D throughout the year.