Rising numbers of neutrophils (left) in the infected lung are the cause of rising histamine (right).

Mast cells together with basophils are considered the major producers of histamine. Because bacterial infection of the lung can lead to asthma attacks more severe than those caused by allergens, Caughey's group hypothesized that histamine might be produced in response to infection and, if indeed it were, that mast cells were likely to be the source.

The team found that, approximately one week after infection with Mycoplasma pulmonis bacteria, histamine levels in the lungs of the mice had risen dramatically. However, this increase was observed even if the mice had no mast cells. The team noticed that the rising level of histamine paralleled an increase in the number of neutrophils in the lung. Considering the possibility that these cells might be the source of the histamine, the team depleted neutrophils in the mast cell-deficient mice and, sure enough, observed a concurrent drop in the level of infection-induced histamine.

Although neutrophils have previously been reported to produce histamine, their contribution was thought to be small. The vast amount of histamine they produce in response to lung infection—an approximately 50-fold induction—was therefore a surprise, says research leader, Caughey.

The team now plans to see whether other bacteria induce a similar increase in the production of histamine, and whether high histamine levels are also a feature of human lung infections. If so, Caughey suggests that antihistamines, not generally considered in the treatment of infection, deserve a second look.