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  • Study identifies potential genetic link to toxoplasmic retinochoroiditis

    By Khalid F. Tabbara, MD
    Uveitis

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    This is the first study to demonstrate the association between the IL-6 (-174G ⁄C) polymorphism and the occurrence of toxoplasmic retinochoroiditis (TR) in humans. Experimental data previously have demonstrated a role for IL-6 in the modulation of acute ocular toxoplasmosis. The results of the current study suggest that genotypes linked to a lower production of IL-6 may be associated with the occurrence of TR.

    IL-6 is a pleiotropic cytokine produced by monocytes, fibroblasts and endothelial cells, as well as the T and B lymphocytes. It is produced by a number of inflammatory stimuli, including antigens, TNF-a, and IL-1 ß. It is known to be produced by both the innate and adaptive immune responses and contributes to differentiation and activation of macrophages and T cells, and terminal differentiation of B cells. IL-6 also drives the differentiation of CD4+ Th2 cells by the induction of IL-4 and acts as a negative regulator of CD4+ Th1 cell differentiation.

    The authors examined 97 patients with TR and 83 healthy blood donors with positive serology for toxoplasmosis but without evidence of retinochoroiditis.

    There was a significant difference in the genotype (P = 0.001) and allele (P = 0.01) distribution between patients and controls. In a sub-group analysis, there was no significant difference in genotype and allele frequency regarding TR recurrences.

    It appears that IL-6 mediated signaling protein results in a marked suppression of inflammatory signal that blocks the generation of protective immunity to Toxoplasma gondii.The role of IL-6 in the regulation of inflammation in TR has been demonstrated in an animal model of acute ocular toxoplasmosis. Following toxoplasma infection, IL-6 knockout mice appear to develop a more severe course of inflammation in the retina when compared to wild type. The increase in the severity of the disease is associated with higher eye parasitism and altered expression of pro-inflammatory cytokines.

    It appears from the current study that selective gene polymorphism of IL-6 may lead to or predispose people to retinal infection by T. gondii but does not influence recurrences of TR. This link between TR and a genotype associated with a lower IL-6 production provides evidence that abnormalities in the genetic control of cytokine levels may play a role in influencing the immune response in TR.