Interleukin-7

Interleukin-7 is a pro-inflammatory regulatory protein secreted by bone marrow stromal cells, thymus cells, keratinocytes, fibroblasts and endothelial cells. The gene encoding interleukin-7 is located on chromosome 8.

The effect of interleukin-6 is mediated by membrane-bound receptors. 2 receptor types are known: receptor type 1 (CD127) is expressed mainly on activated T-lymphocytes. Receptor type 2 is expressed on non-stimulated T-lymphocytes. Besides the membrane-bound receptors, a soluble receptor (sILR-7) circulating in the blood plasma was found, which probably regulates the biological activity of interleukin-7 in the sense of a feedback mechanism.

Receptors for interleukin-7 are also found on macrophages, on pre-B lymphocytes and their precursors, but not on mature B lymphocytes. The IL-7 signalling pathways involve the phosphatidyl inositol-3-kinase (PI3K) signalling cascade, the Ras/Raf signalling cascade and the Januskinase/STAT signalling cascade.

In activated T lymphocytes, the formation of interleukin-3 and GMCSF is stimulated. In monocytes, Il-7 mediates the formation of inflammatory mediators such as interleukin-1, interleukin-6 and the "macrophage inflammatory protein". With regard to the influence of interleukin-7 on osteoclastogenesis, both inhibitory and activating influences have been demonstrated.

The cytokine can control the proliferation of malignant processes by influencing the "microenvironment" of a tumour and its immune system. The role of interleukin-7 and 15 has been studied extensively in hematological tumors. The cytokine was found elevated in lymphomas and leukemias. Furthermore, interleukin-7 is produced by various solid tumors, but the influence of the cytokine on tumor cell proliferation is unclear. Elevated interleukin-7 is associated with a poor prognosis in breast cancer. Elevated levels of interleukin-7 and interleukin-15 have been shown to occur in the early stages of prostate cancer. Other malignant tumors are associated with variously elevated interleukin-7 levels: renal carcinoma, neuroblastoma, glioma, colorectal carcinoma, bronchial carcinoma, etc. Inhibition of the interleukin-7 receptor blocks B- and T-cell development.

Elevated levels of interleukin-7 are found in acute "graft-versus-host disease" and can be seen as an indicative factor for early therapy.

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