Man flu is real, reported the Daily Mirror . Many newspapers reported the news that scientists have found men suffer from flu more because they “invest in their spirit of adventure at the expense of their immune system” (The Daily Telegraph ).
The news is based on a mathematical model developed by Cambridge researchers, which they themselves found surprising. They say that if males are more exposed to infection than females, perhaps through riskier behaviours, it is possible that they evolve less effective immune systems. They say that this result is at “odds with intuitive expectations”.
Many newspapers have reported this story, some putting forward additional theories of how testosterone might interfere with immunity. In general, surprising findings from models should be treated cautiously, and any plausible theory of an immune difference between the sexes will need testing in real-life studies. For now, man flu (different responses between the sexes to flu) remains unproven.
Where did the story come from?
This research was carried out by Dr Olivier Restif and Dr William Amos from the departments of Veterinary Medicine and Zoology at the University of Cambridge. The study was supported by a Royal Society University Research Fellowship to Dr Restif and published in the peer-reviewed journal, Proceedings of the Royal Society, Biological Sciences .
The study generated much interest in the media, which reported many of the underlying theories put forward by the authors to explain their findings. The Daily Mail puts forward an idea by Dr Restif that vaccination campaigns could take into account men’s greater vulnerability, however this suggestion goes well beyond what might be inferred from the science as no actual difference has been demonstrated in the study.
What kind of research was this?
This was a mathematical modelling study, in which the researchers tried to answer the question “why do males and females often differ in their ability to cope with infection?”.
The researchers introduce the topic by discussing some animal studies that have already indicated there may be differences between the sexes. These include suggestions that:
- Males are more exposed to infection risk than females.
- Males are less able than females to deal with infection.
- Males shed more viral particles.
- Males suffer more severe symptoms.
They note that not all the study findings agree with each other. They also point out that in some animals the female is at higher risk of infection. This study investigated both how men and women choose partners (reproductive strategies) and how they react to different pathogens, such as viruses.
The researchers developed six models in all. Three models assumed that there was no difference between males and females in susceptibility to infection and three assumed that there were. The models varied in the ‘assumed values’ and ‘trade-offs’ (the theoretical choices made) between recovery rates, background death rates and the ability to reproduce for men and women. According to the researchers’ predetermined equations, as one of these values increased, another decreased.
One of these six models was designed to assess recovery rate from infection. This model assumed men were more susceptible to infection than women, and then made a ‘trade-off’ between recovery rate and death rate. It is this model that produced 'surprising' results.
What did the research involve?
The modelling in this study ran through two parts (equations). The first calculation was aimed at giving some insight into how genes (genotypes) are passed down through multiple generations and how the proportions of children carrying the variations of a gene can change under ideal conditions. The second part looked at how the numbers of people in a population of susceptible men and women might increase or decrease as a result of three different assumptions about recovery rates, death rates and ability to reproduce.
The values entered into these equations were arbitrary, designed to test how the model behaved rather than come up with a definitive answer.
The researchers then used a computer program to look at ‘evolutionary stable strategies’. This is a technique used in the field of behavioural ecology for comparing the relative selective pressures that females and males are subjected to. In this study, the researchers used their model to predict when males and females might become equally exposed to, and affected by, infection.
The researchers adjusted the model for the effect of intra-sex competition on reproductive success - by assuming that males are competing for access to females, whereas females are competing for resources.
What were the basic results?
The researchers report how the model responded to several different assumptions. They say that for one of the three situations where the model assumed there were differences between the sexes in susceptibility to infection, males with higher susceptibility or exposure to infection evolved lower immunity.
This modelled increase in male susceptibility (or exposure) to infection favoured the spread of the pathogen in the whole population and led to higher resistance or tolerance in both sexes. However, above a certain level of exposure, the benefit of rapid recovery in males was lessened due to constant re-infection (assuming there was no acquired immunity in the population).
This means that in one model (the one that assumed that males had a lower resistance to infection), males ultimately evolved a lower immunocompetence (ability to fight off infection).
How did the researchers interpret the results?
The researchers say their results show that, under a range of “genetic and ecological assumptions [constraints], males and females can evolve different levels of immune defences, sometimes at odds with intuitive expectations”.
They claim to have identified some of the key factors that help to understand the selective or evolutionary pressures involved.
As with all modelling studies, the results depend on the underlying assumptions, and in this case on the way that the researchers have made mathematical links between recovery rates, death rates and the ability to reproduce, in the theoretical population.
There are other theories that the male immune system may be influenced by testosterone, which the researchers did not consider. They also did not measure immunity in men or women. In addition, the researchers do not suggest in their research paper that their model has any implications for human health.
- One of the six models begins with the assumption that men have a higher susceptibility to infection. The results of this model have been reported as supporting the case for man flu. However, the finding is purely hypothetical at this stage and results from demonstrating that, under certain assumptions, these men will lose more of their ability to fight off infection.
- The assumption that immunity is inherited in a ‘Mendelian’ way or by a single gene, is just that, an assumption. Much more research would be needed to test if this is actually the case.
- The fact that sexual selection (how the choice of a partner may influence the inheritance and prevalence of certain traits) was not included in this model is a limitation to the study. The researchers acknowledge this and hope to include this in future models.
Overall, this modelling study suggests several possible patterns for how immunity might be inherited differently among the sexes - however, these are only theories. Headlines that ‘man flu’ is real and not a myth are unjustified. Any plausible theory of an immune difference between the sexes would need testing in real-life studies, ones that also include assessment of the difference within each sex grouping, too.