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Mounting evidence that the immune systems of men and women work differently isn't being taken into account by pharmaceutical companies when they develop new drugs, a leading Canadian immunologist says.

Eleanor Fish, a professor at the University of Toronto, says this means women may be taking prescription drugs that aren't as effective for them as they are for men, and are at greater risk of suffering from adverse drug reactions from medications already on the market.

For example, she says, a number of studies have shown that women have more frequent and serious adverse events from anti-retroviral therapies used to treat HIV-AIDS.

In an article in the latest edition of the journal Nature Reviews Immunology, Dr. Fish calls on the medical community, including drug companies, to start taking sex-based immune-system differences more seriously.

"It's a wake-up call," she said. "When we develop drugs and diagnostics, we fail to adequately recognize these differences."

Dr. Fish, who holds a Canada Research Chair in Women's Health and Immunobiology, says we all have a wide array of immune-system cells that respond to infections and wounds or that attempt to clear tumours from our bodies.

But the profile of that immune response is different in men and women, Dr. Fish says.

In general, men are more susceptible to viruses and bacteria and tend to develop more severe infections. Women, however, are more likely to develop autoimmune diseases like rheumatoid arthritis or lupus.

The stage a woman is at in her menstrual cycle can influence how her body responds to invading bacteria, viruses and parasites, such as the one that causes malaria.

It is complicated, because estrogen levels affect different types of immune-system cells in different ways. Oral contraceptives may also have an impact.

Yet pharmaceutical companies don't enroll enough women in clinical trials to get an adequate assessment of how this might affect how well a drug works for women compared to men, Dr. Fish says.

"Women remain underrepresented in clinical trials," she said.

In 1998, the U.S. Food and Drug Administration required that new drug applications include data on the safety and effectiveness of the product on each sex. "So far, however, there has been inadequate compliance to these policies," Dr. Fish said.

In 2005, she writes in her paper, eight out of 10 prescription drugs withdrawn from the U.S. market were pulled because of health issues in women.

Some of her colleagues at other universities say Dr. Fish is raising an important point. Katrina Gee, an immunologist at Queen's University in Kingston, Ont., who studies HIV-AIDS, says the article contains compelling information for scientists to investigate further.

Dr. Gee says sex-based immune-system differences "may have an important bearing on treatment options."

But others, such as Kent HayGlass, an expert in allergies at the University of Manitoba who holds a Canada Research Chair in Immune Regulation, says researchers are not ignoring sex-based differences in immune function. There have been a large number of studies, he says, including many cited by Dr. Fish in her article.

Sex-based differences aren't the only factor affecting immune-system function. Ethnicity, age and socioeconomic factors also affect how well immune systems respond to invaders, and require more study.

Dr. Fish and her colleagues are starting a long-term project at the University Health Network in Toronto that may solve some of the mysteries about the different ways people fight disease.

The gene pool

The differences between men's and women's immune systems are not all related to hormones.

Women carry two copies of the X chromosome, while men have only one and a much smaller Y chromosome.

So far, roughly 60 genes linked to the immune system have been identified on the X chromosome. If women have a mutation in one of these genes, they have a backup copy. Men don't.

These kinds of differences may prove to be crucial in treating outbreaks of new infectious diseases, says Eleanor Fish, an immunologist who worked on severe acute respiratory syndrome, or SARS, during the 2003 outbreak.

Women had a lower mortality rate from SARS than men, Dr. Fish says, possibility because their immune responses were more robust. Anne McIlroy