M´ etodos Cuasipart´ıcula

Uveitis may be restricted to the anterior segment, involve the anterior segment and anterior vitreous, or predominantly affect the posterior segment with or without signs o f inflammation within the AC. The varying manifestations of uveitis may represent the spectrum of intraocular inflammation in response to different insults be it infectious or non-infectious. The spectrum can vary from uveitis that are acute in nature with explosive recurrent attacks like Behçet's disease to the chronic low grade uveitis as in FHC. PS or adherence o f the iris to structures posterior to it develops in all severe untreated anterior uveitis. This may result in pupillary block and occlusion of the angle by forward movement of the peripheral iris leading to pupillary block glaucoma with significant ocular morbidity. Interestingly this complication does not develop in-patients with FHC despite the ongoing chronic inflammation. These differences in clinical manifestations may be due to different triggering or effector mechanisms in the various types o f uveitis. The former is difficult to ascertain in human diseases as opposed to animal models of uveitis. However the latter could be dissected by studying the effector molecules produced during active uveitis such as cytokines.

The important role of T cells in uveitis has been well demonstrated by several workers (Chan, 1985; Chan, et al., 1985; Nussenblatt & Scher, 1985; Lightman & Chan, 1989; Lightman & Chan, 1990). The pathogenic mechanism is believed to due to cell-mediated immunity with the predominant role of T cells

and other accessory cells of the immune system. Apart from the T cells, which are specific effectors of immunity, other cells play their role in the amplification o f immune response leading to uveitis. In some form o f cell mediated immunity, antigen-specific T cells directly perform the effector function, as when CTLs lyse specific target cells; in other types, antigen-activated T cells secrete cytokines which are soluble mediators of innate and specific immunity that recruit and activate effector cells that are not specific for the antigen, such as macrophages and NK cells.

In general cytokines are synthesised in response to inflammatory or antigenic stimuli and act locally, in an autocrine or paracrine fashion by binding to high affinity receptors on target cells. Cytokines mediate many o f the effector functions o f cells that produce them and are the principal mechanisms by which various immune and inflammatory cell population communicate with each other. Hence by means o f cytokine secretion T cells stimulate the function and focus the activity o f non-specific effector cells o f innate immunity, thereby converting these cells into agents of specific immunity.

Cytokines, which can be regarded as biologic response modifiers, can be classified into three groups according to their principal actions (Abbas, et al., 1996). The first group consist o f those cytokines that mediate innate immunity and includes anti-viral cytokines (e.g. type 1 interferons, IL-12, IL-15), proinflammatory cytokines (TNF, IL-1, IL-6, and chemokines) and regulatory cytokines (e.g.IL-10). The predominant cellular source o f these molecules is mononuclear phagocytes.

The second group o f cytokine is derived from antigen-stimulated T lymphocytes and serves to intensify, focus and specialise inflammatory reactions of specific immunity. This group includes IL-2, the principal T cell growth factor, IL-4, the principal switch factor for Ig-E, currently known as a major regulator o f Ig-E and mast cell/eosinophil mediated immune reaction, and TGPp which inhibits lymphocyte response and function as “anti-cytokine” by its antagonising effect on proinflammatory cytokines. Another T lymphocyte derived cytokine is IFNy, the principal activator o f mononuclear phagocytes in addition to TNFp, an activator o f neutrophils, and IL-5 an activator of eosinophils.

CD4^ T cells may differentiate into specialised effector Th 1 that secrete IFNy and TNFp, which favours cell-mediated-immunity, or into Th 2 cells that secrete IL-4, and IL-5, which favours Ig-E and eosinophil mediated immunity. The pattern o f differentiation may be influenced by cytokines produced in the innate response or early in the specific immune response (Trinchieri, 1995). Although Th 1 and Th 2 cells are major sources o f their respective cytokines, many other cells within and outside the immune system also produce these cytokines. Subsets o f T cells, CD4^ and CD8^ T cells can all secrete Th 1 or Th 2 like cytokine patterns. NK cells produce IFNy and TNFa, and contribute to Th 1 like responses (Trinchieri, et al., 1992). IL-10 is produced by macrophages, kératinocytes and cytotrophoblast cells in the placenta. Since several cell types may contribute to an overall Th 1 or Th 2 cytokine pattern, the term typel (for cell mediated immunity) and type 2 (for humoral immunity) is preferred.

The third group of cytokine consists of cytokines derived from marrow stromal cells and T cells, which stimulate the growth o f bone marrow progenitors, thereby providing a source o f additional inflammatory leucocytes. These are collectively called colony-stimulating-factors. Hence the cytokines serve many functions and provide links between specific and innate immunity.

Many previous studies have quantitated various cytokines in the AH (Hoekzema, et al., 1990; Murray, et al., 1990a; Murray, et al., 1990b; Hoekzema, et al., 1991; de Boer, et al., 1992) and in this study more cytokines which regulate both innate (IL-12, IL-10, TNFa) and specific immunity (IL-2, IL-4, IFNy, TGFp) have been quantitated. The levels o f these cytokines in the AH of uveitis patients are compared with levels in AH o f control patients. In addition the cytokine pattern in these AH was determined to ascertain any correlation between the clinical manifestations and the cytokine levels.