Towards cytokine insight in sight.

Commentary Towards cytokine insight in sight In a recent paper in the Lancet,' antibodies that neutralise the cytokine, tumour necrosis factor a (TNF-a), were reported to produce marked and somewhat sustained relief of symptoms in the immune mediated disease rheumatoid arthritis. This report lends hope that the neutralisation of cytokines may eventually be of therapeutic value in inflam-matory eye diseases including uveitis, keratitis, scleritis, comeal transplant rejection, cystoid macular oedema, and possibly fibrotic or angiogenic diseases including diabetic retinopathy, proliferative vitreoretinopathy, macular degeneration, pterygium, and fibrosis after surgery to reduce intraocular pressure. In order to consider the challenges and potential of cytokine inhibition, it is necessary to review several principles about cytokines and cytokine function. Cytokines are proteins that cells use for communication. The cells in the immune system utilise cytokines extensively. The cytokines include an expanding family of at least 15 interleukins, the tumour necrosis factors, chemokines, colony stimulating factors, interferons, and a variety of growth factors such as transforming growth factor 1B (TGF-P). Lipids, nitric oxide, and peptides are usually not considered cytokines although these substances, too, are involved in cellular communication. The rationale to target cytokines is simple. Cytokines are essential for the function of the immune system. Many diseases result from a pathological immune response. Therefore, interrupting the cytokine communication will result in diminished inflammation. Furthermore, a variety of cytokines including interleukin-1 (IL-1), TNF-a, IL-6, IL-8, IL-2, and granulocyte macrophage colony stimulating factor can be directly injected into the eye with significant inflammation resulting.2 On the other hand the direct injection of IL-10 or TGF-1 may be anti-inflammatory. Several basic principles with regard to cytokine function may help us to understand the complexity of the challenge in interfering with cytokine control. First of all cytokines are pleiotropic. This means that they have may targets and regulate many genes. For example, among other functions, IL-1 stimulates fibroblast growth, increases collagen synthesis , causes bone resorption, is cytotoxic for some tumour cells, is chemotactic for lymphocytes, stimulates prostaglandin synthesis, causes basophil histamine release, induces fever, and stimulates synthesis of other cytokines. Secondly, cytokines often share functions-that is, they are redundant. For example, both IL-1 and TNF can activate lymphocytes, act as pyrogens, cause muscle cachexia, induce the acute phase protein synthesis, activate endothelial cells, cause fibroblast proliferation, and induce tumour necrosis. Thirdly, cytokines function within a network. Consequently the antagonism of a single cytokine may alter many downstream …