MAINZ, GERMANY—Interleukin 10 (IL-10) is thought to play an important role in the body’s defense against contact allergens, but results of a new study suggest that it may be even more crucial to that defense than was originally thought.[1] The findings could eventually give rise to an IL-10–based therapy for contact allergy.

Marcus Maurer, MD, and colleagues showed that low-zone tolerance (LZT) to contact allergens is IL-10–dependent in mice. Specifically, IL-10 is essential for generation of the CD8+ effector T cells required for LZT.

“We call these CD8+ cells preventive T cells because they are the only cells we know of that can prevent the development of, rather than merely suppress, other effector T cells involved in the immune reaction to contact allergens,” noted Dr. Maurer, an Assistant Professor of Dermatology at the University of Mainz. “It is a very elegant way for the skin to maintain a low degree of sensitization to contact allergens,” he remarked.

REPEATED ALLERGEN APPLICATION

To determine IL-10’s importance in the development of LZT, the investigators repeatedly pretreated the ears of mice with low doses of the contact allergen trinitrochlorobenzene (TNCB) or a control substance; they then applied a single TNCB dose large enough to induce contact hypersensitivity. The study was performed on wild-type mice, as well as on mice genetically deficient in IL-10.

LZT was assessed by measuring the thickness of the skin on the mice’s ears. Small amounts of swelling suggested normal tolerance, whereas substantial swelling indicated a lack of LZT.

After the high-dose challenge, the IL-10–positive mice developed normal LZT; they displayed markedly less swelling than did the mice lacking that cytokine. In contrast, the amount of swelling in the IL-10–deficient mice not only was much greater but also was virtually identical regardless of whether pretreatment included low-dose TNCB or not. This result, said Dr. Maurer, proves that LZT is impossible without IL-10.

TREATMENT IMPLICATIONS

Contrary to the investigators’ expectations, treating IL-10–deficient mice with that cytokine during the high-dose TNCB challenge did not result in normal LZT. However, giving them IL-10 during repeated low-dose TNCB applications restored their tolerance to normal. This suggests that LZT has two successive phases: an induction phase, during which IL-10 is needed, and an effector phase, which is IL-10 independent.

Appropriately timed treatment with the cytokine also benefited the IL-10–positive mice. Without IL-10 administration during pretreatment, these mice reduced their inflammatory response to TNCB by 60% to 70%. With cytokine pretreatment, the inflammatory response was reduced by 96%.

Of course, successful treatment in animals does not always translate to ready use in humans. Therefore, the next step, stressed Dr. Maurer, is to study the effectiveness of IL-10 in healthy persons at risk for contact allergy. If such trials are successful, he said, “we hope that someone will eventually make IL-10 into a preventive therapy for those at high risk for contact allergy.”

—Timothy Begany