What gives you fever?

A genetic defect that scientists believe causes familial Hibernian fever, a rare condition mostly affecting people of Irish and Scottish decent, could provide new clues to the elusive mechanisms that trigger inflammation in more common diseases such as rheumatoid arthritis and lupus.

A report, published earlier this month in the journal Cell, pinpoints a gene, tumour necrosis factor receptor (TNFR1), which makes a protein that is shed into the blood neutralising tumour necrosis factor (TNF). The unopposed action of TNF is thought to promote episodes of inflammation that are characteristic of Hibernian fever. People with the condition, says the new research, appear to have mutations in the TNFR1 gene, which means the protein is not properly shed into the blood, resulting in serious inflammation.

"The disease, which we now call TRAPS - TNRF1-associated periodic syndrome - varies in its seriousness," explains Michael McDermott of Queen Mary and Westfield College, London, one of the researchers in the international team involved in the study to pinpoint the mutation in the gene.

"It ranges from mild pain coming on in the mid-20s, to debilitating stomach pain and very high fever for weeks to months on end. It can be like having flu for months at a time, and episodes can recur throughout a person's life."

Until now, steroids have been the only treatment available.

"Now that we know that TRAPS is in part caused by a problem in the receptor shedding process, we can work towards the development of TNR1 replacement therapy," McDermott says. "This has already been tested on inflammatory diseases in the United States, with very promising initial results."

The next step for researchers is to see whether the mutated TNR1 molecule is implicated in other inflammatory diseases, such as lupus and rheumatoid arthritis.