The molecule interleukin-7 (IL-7) is an important immune system messengers that a sufficient number of T cells guaranteed at present in the body's defenses. ETH Zurich researchers have now shown that IL-7 has another important function: it improves the function of the lymphatic drainage collect moisture that has leaked from the blood vessels into the body tissues and back into the bloodstream. In the future, these insights for lymphedema patients, the lymphatic system is not working properly useful, what tissue to become fluid retention and swelling.

The predisposition to the development of lymphedema can on the one hand, are hereditary. On the other hand, lymphedema often. During the period after a tumor operation Primary tumors are surgically excised tumor and lymph nodes are often removed because they can contain metastases. Tumor in the course of such a surgical procedure is the lymphatic tissue is damaged. This tissue fluid is often not properly arranged, so that the occurrence of lymphedema in 20 to 30 percent of patients.

No drug treatment yet

Currently wearing the only treatment options for patients with lymphedema compression stockings and undergoing a medical manual lymphatic drainage massage therapist. "In IL-7, we have a molecule and a mechanism for improving lymphatic drainage for lymphedema therapy, useful to be discovered," says study leader Cornelia Halin, Assistant Professor of Drug Discovery Technologies.

In their study, the researchers found that IL-7, which shape is formed by the so-called endothelial cells. The lymphatic vessel wall These cells also bear receptors, IL-7 in a certain way based on the lock-and-key principle. "Although we have not formally proven that so far, we assume that the lymphatic endothelial cells produce the neurotransmitter, may directly affect their own function," says Halin. To date, IL-7 is one of only a few molecules have been identified that support lymphatic drainage. A few years ago, researchers discovered that the other endogenous growth factor VEGF-C, a molecule of interest in this context is perhaps also.

Findings from an animal model

Halin and her colleagues showed the drainage support function of IL-7 by drainage experiments in mice, where blue, albumin-binding dye in the skin of the mouse injected ear. It is noteworthy that albumin, a naturally occurring protein that is transported from the tissues via the lymphatics. By quantifying the dye in the tissue remained one day after the injection, the researchers were able to determine how well worked the lymphatic these animals.

In carrying out this experiment, mice, in which a functional IL-7 receptor, it is noted that these mice to only remove half the dye out of the ear skin in order to compare with a functional mouse IL-7 receptor. However, they observed a significant increase in lymphatic drainage in mice with increased IL-7 production. Finally she IL-7 protein is in a third experiment, unchanged administered healthy mice and found that a therapeutic treatment done to improve lymphatic drainage function.

Been tested in patients

The researchers are now planning similar experiments in mice in which lymph vessels are surgically destroyed, similar to the situation in patients after cancer surgery. Here, the researchers want to test whether treatment with IL-7 or IL-7 could lymphedema would be prevented. Reduce the existing lymphedema administered

The long-term goal is to explore the potential of IL-7-based drugs for lymphedema. In particular, IL-7 has been tested in clinical trials, although for different indications: due to its immune-stimulatory activity on T cells, IL-7 is currently undergoing in patients with immunodeficiency diseases such as HIV or hepatitis infection or bone marrow tested transplants.

A new report suggests that the concentration of one human cytokine, interleukin 7 (IL-7), in the semen of HIV-1-infected men may be a key determinant of the efficiency of HIV-1 transmission to an uninfected female partner. In their study published February 7 in the Open Access journal PLOS Pathogens, a research group from the Eunice Kennedy-Shriver National Institute of Child Health and Human Development (NICHD) led by Leonid Margolis report that the increased IL-7 concentration in semen facilitates HIV transmission to cervical tissue ex vivo.

Semen is a complex biological fluid containing not only spermatozoa but also cytokines, a group of extracellular proteins that modulate immune responses. As a result of HIV infection, the concentrations of various cytokines in semen is profoundly modified, in particular the concentration of interleukin 7 (IL-7) is greatly increased. Despite this evidence of strikingly elevated IL-7 levels in seminal plasma, there was limited knowledge about any effects this cytokine might have on HIV-1 sexual transmission.

To investigate the question about the effects of this increased IL-17 on HIV-1 sexual transmission, Andrea Introini and colleagues from the Margolis lab developed a system of explants of cervico-vaginal tissue that can be maintained outside of the body in culture for up to two weeks while preserving the cytoarchitecture of the tissue. In this system, HIV transmission can be simulated and studied under controlled laboratory conditions. When researchers added IL-7 in concentrations comparable to that found in the semen of HIV-1 infected men, HIV was transmitted more efficiently and replicated to a higher level than without IL-7. Normally, HIV-1-infected cells quickly die as the result of apoptosis, a programmed death triggered by HIV infection. IL-7 inhibits apoptosis of infected cells, allowing them to produce more virus and thus increasing the chances of the incoming virus to disseminate through the tissue. Also, IL-7 stimulates T cell proliferation, thereby also providing to HIV even more potential targets to infect.

The authors speculate that IL-7, together with other cytokines, may determine sexual transmission rates of HIV-1 and that changes in the seminal cytokine load may explain differences in HIV transmission from different individuals. However, whether the effect of IL-7 that has been demonstrated ex vivo occurs also for sexual partners in vivo, is a subject for future research. If this increase does occur in vivo, then it should be investigated whether HIV-1 infected individuals that have been treated systemically with IL-7 in order to increase their T cell counts may have also resulted in the unintended increase of their seminal IL-7 levels. Finally, this study suggests that seminal cytokines may become new targets for HIV-preventive strategies.