Cytokines and immunopathogenesis of intraocular posterior segment inflammation

Abstract

Summary Intraocular inflammatory eye disease remains a significant cause of visual handicap in the working age population within developed countries. The development of inflammation is unquestionably multifactorial, including genetic susceptibility, nutritional status, innate stimuli such as injury and concomitant ocular and systemic infection, and presence of autoreactive T cells. When no overt infectious agent is identified in uveitic patients, we presume that autoimmunity is the underlying pathogenesis. Although retinal antigen-specific Th1 CD4 + T cells mediate experimental models of posterior uveitis, confirmation of such in man has yet to be fully established. Antigen is the initiator of all acquired immune responses, whereupon the primary function of the immune system is to recognise exogenous antigens and eliminate pathogens. Additionally, the maintenance of immune regulation is brought about by tolerance to self-antigens acquired during development (central tolerance) or actively during adult life (peripheral tolerance) and in the case of exogenous antigens (viral and bacterial) immune responses are, in part, kept in check by inhibitory cytokines and soluble cytokine receptors. The dynamic and continual regulation of immune responses is orchestrated by cytokines, controlling leukocyte behaviour and activation including antigen-presenting cells (dendritic cells; DC), antigen-specific T cells, and non-specific leukocytes such as macrophage and granulocytes. Moreover, tissues such as the eye are endowed with powerful immunomodulatory mechanisms, in which cytokines play a pivotal role to control immune responses, limit tissue damage, and restore homoeostasis.