Interleukin-1's secret message to ACTH.

Interleukin-1's secret message to ACTH 

Two decades after scientists began studying the link between immunity and stress, three new reports strengthen the idea that the protein interleukin-1 (IL-1) carries regulatory signals between the two systems. Conflicting scientific data, however, show that the way in which this messenger service operates is still unclear; scientists do not know whether or not IL-1 acts directly on the pituitary, the body's so-called "master gland' nestled under the brain.

A related protein, interleukin-2, has received more attention because of its reported success in treating cancer (SN: 1/17/87, p.44). But studies have shown that IL-1, also secreted by immune system cells, has broad influence within the body. During stress from infection or trauma, it induces fever, inflammation and the need to sleep--all important in healing.

In addition to its immune system functions, IL-1 apparently can induce the pituitary gland to secrete adrenocorticotropic hormone (ACTH) into the bloodstream. Activated by the circulating ACTH, the adrenal glands--which lie atop the kidneys--release other hormones that affect the stress response. In this capacity, IL-1 becomes a primary chemical signal between the body's immune and hormone-release systems during physical, and perhaps emotional, stress.

The three studies reported in the Oct. 23 SCIENCE attempt to clarify whether IL-1 acts directly on the pituitary gland in ACTH release, or acts indirectly by triggering the brain's hypothalamus to secrete chemicals that then activate ACTH release from the pituitary. But the results are contradictory, and while they add insight to IL-1's role in ACTH release, they fail to explain how that process works.

Researchers at Stanford University and the Salk Institute in La Jolla, Calif., incubated pituitary cells from rats with either human or mouse IL-1, and then measured the levels of ACTH in the cultures. Stanford's Robert Sapolsky and his colleagues report that IL-1 did not cause ACTH secretion. But the cells did secrete ACTH when they repeated the experiments using corticotropin-releasing factor (CRF) instead of IL-1. This factor is produced by the hypothalamus region of the brain the presence of the interleukin.

This, say the scientists, is evidence that IL-1 does not act directly on the pituitary, but instead acts on the brain, which then sends CRF to the pituitary as a secondary messenger to switch on ACTH release. Those findings are supported by a report, also in SCIENCE, from researchers at Free University in Amsterdam, the Netherlands, and at Schweizerisches Forschungsinstitut in Davos-Platz, Switzerland--the group that first reported in 1986 that IL-1 from the immune system somehow induces ACTH secretion during stress.

However, scientists at Walter Reed Army Institute of Research in Washington, D.C., report in the same issue that human IL-1 does stimulate cultured rat pituitary cells to release ACTH. But "the apparent conflicting results' may be two sides of the same coin, says Michael D. Lumpkin of Georgetown University in Washington, D.C. In an accompanying commentary, Lumpkin points out that there are two structural forms of IL-1, and that one may activate the brain, while the other affects pituitary function. Another intriguing possibility, he says, is that the results may reflect sex differences between the pituitary-cell donors used for the studies, since there is evidence that estrogen makes cells more susceptible to substances that stimulate the release of ACTH.

"What's clear to everyone is that the immune system can turn on the stress response,' Sapolsky told SCIENCE NEWS. "But everyone's grappling with the mechanism.' He also wonders about the "logic' behind the IL-1/ACTH connection, given that some hormones have been shown to decrease immunity. "Why, during stress, should you want to suppress the immune system?' he says. "It is a fascinating issue, because people under stress get sicker more often.'