IL-1 is an important regulator of hematopoiesis, although the phenotype of IL-ip-deficient mice is remarkably normal. IL-1 induces the production of CSF by bone marrow stromal cell and receptors for CSF. Thus IL-1 synergizes with CSF to stimulate growth of early hematopoietic bone marrow progenitor cells and can counteract the myelosuppress-ive effects of radiotherapy and chemotherapy. The latter effect is mediated partly through the induction of mitochondrial manganese superoxide dismutase activity that scavenges potentially toxic superoxide radicals.
IL-1, an endogenous pyrogen, acts on the fever center and also stimulates the hypothalamus to produce corticotropin-releasing hormone (CRH), resulting in the release of adrenocorticotropic hormone (ACTH) from the pituitary. IL-1 can also directly stimulate pituitary ACTH release. This activation of the HPA axis culminates in induction of the production of glucocorticoids by the adrenals. Glucocorticoids act as a negative feedback regulator by suppressing the production of IL-1 and upregulat-ing both type I and type II IL-1 receptors. IL-1 also inhibits the release of both gonadotropin-rcleasing hormone and luteinizing hormone (LH), as well as thyroid-stimulating hormone (TSH) and decreases plasma thyroid hormone.
IL-1 is postulated to play a major role in destructive joint disease such as rheumatoid arthritis. It regulates bone resorption by inducing metalloprote-ase secretion by chondrocytes, resulting in cartilage breakdown and proteoglycan release. IL-I stimulates fibroblast proliferation and secretion of collagenase, IL-6, IL-8 and G-CSF. It induces cyclooxygenase synthesis and hence prostaglandin release from fibroblasts, but suppresses expression of mRNA for matrix proteins.
IL-1 can have antitumor as well as tumor growth promoting effects. IL-1 has been shown by Onozaki and coworkers to act both as an in vitro cytostatic and a cytocidal agent for a number of tumor cell lines. This activity is associated with inhibition of ornithine decarboxylase activity by II-1. II.-l increases natural killer (NK) cell activity and T cell-dependent tumor immunity in vivo. Fibrosarcoma tumor cell lines transfected to overexpress IL-lct have been shown by Apte and colleagues to be more readily rejected and to induce the development of immune resistance upon rechallenge. However, systemic administration of IL-1 has been reported to promote the development of tumor metastases in some animal models. Thus under some circumstances IL-1 appears to promote tumorogenesis.
Was this article helpful?
Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.