Review Article THE ROLE OF CYTOKINES IN THE PATHOGENESIS OF INFLAMMATORY EYE DISEASE Denis Wakefield” and Andrew Lloyd A coherent view of the role of cytokines in inflammatory eye disease is emerging as a result of studies both in man and experimental animals. Cytokines have been demonstrated in ocular tissue obtained from patients with intraocular inflammation (uveitis) (gamma interferon, IL-2) and have been shown to induce inflammation in experimental animals after intraocular injection [(IL-l, IL-6, IL-S, tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF)]. Several unique features of the immunology of the eye such as the immunosupression associated with anterior chamber associated immune deviation (ACAID) may be due to the effects of cytokines. Similarly, common complications of ocular inflammation such as glaucoma, keratic precipitates, retinal (macular) oedema and neovascularization may be mediated by cytokines. Understanding of the role of cytokines in inflammatory eye disease has the potential to lead to the development of therapies to abrogate the effects of these important mediators of the inflammatory response. Inflammation of the eye is a,common clinical prob- lem that may involve any part of the eye. The uvea, the middle coat of the eye, takes the brunt of most serious ocular inflammation as a result of its extreme vascular- ity. Uveitis is a complex group of diseases resulting from diverse aetiologies and pathogenic mechanisms, the study of which has provided increasing insight into the role of cells and biologically active mo)lecules in the immunopathogenesis of these diseases. Uveitis is a leading cause of visual impairment and blindness in most countries.lS2 It is characterized by acute, recurrent or persistent inflammation that may effect the anterior (anterior uveitis, AU) or posterior uvea (posterior uveitis, PU). Despite extensive investigation, uveitis re- mains an idiopathic disease in the vast majority of From the Laboratory of Ocular Immunology, School of Pathology, University of New South Wales, P.O. Box 1 Kensington. NSW 2033, Australia. I *To whom reprint requests should be addressed. Received 10 July 1991; revised and accepted for publication 17 September 199 1. Q 1992 Academic Press Limited 1043-4666/92/010001 +OS $05.00/O KEY WORDS: cytokines/eyes/inflammation/uveitis CYTOKINE, Vol. 4, No. 1 [January), 1992: pp 1-5 cases.‘.2 Recent evidence from studies in human uveitis and animal models, including experimental autoim- mune uveitis (EAU) induced by several different retinal antigens, and endotoxin-induced uveitis (EIU) induced by lipopolysaccharide (LPS), has significantly in- creased our knowledge of the pathogenesis of ocular inflammation. There is considerable experimental evidence for the concept that T cells and cytokines play a major role in the pathogenesis of uveitis. First, T cells have been demonstrated to be the most abundant cell type in the uveal tissue, retina, aqueous and vitreous humor of patients with uveitis3 T cells are also the principle cells implicated in the pathogenesis of retinal-S antigen-in- duced EAU.4 Adoptive transfer experime’nts have re- vealed that T lymphocytes, and not serum, can transfer this disease.4 Inflamed uveal tissue demonstrates in- creased HLA class I and class II antigen expression, probably induced by cytokines.5-7 Interleukin 2 (IL-2) has been detected in inflamed uveal and retinal tissue and IL-2 receptor levels are increased in patients with certain types of uveitis.’ Finally, the dramatic suppress- ive effect of cyclosporin-A in controlling uveitis has been repeatedly demonstrated in EAU and human disease.g**O This immunosuppressive drug is known to inhibit the synthesis of several cytokines, particularly 1