Other biological activities of IL1

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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.

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