Purchase this article with an account.
R.D. Dix, C.O. Ekworomadu, S.W. Cousins; Intraocular Levels of IFN-, but Not TNF-, Decrease During the Progression of Experimental MAIDS-related MCMV Retinitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4617.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We hypothesized that intraocular levels of proinflammatory cytokines IFN-γ and TFN-α decrease during the evolution of AIDS-related CMV retinitis. This hypothesis was tested by measuring intraocular INF-γ and TNF-α levels at various times during the progression of MCMV retinitis in mice with MAIDS, a retrovirus-induced immunodeficiency syndrome that exhibits systemic changes in Th1 and Th2 cytokine expression at ~3 wks after initial retrovirus infection. Methods: Left eyes of groups of normal C57BL/6 mice or C57BL/6 mice with MAIDS of 2 wks (MAIDS-2), 4 wks (MAIDS-4), and 12 wks (MAIDS-12) duration were infected with MCMV by subretinal inoculation; contralateral eyes served as uninfected sham-inoculated controls. MCMV-infected and control eyes were collected from all animals at 5 days postinfection, homogenized, and subjected to a cytometric bead array analysis for measurement of mouse IFN-γ and TFN-α (pg/ml/eye). MCMV-infected eyes were collected at 10 days postinfection from parallel groups of normal and MAIDS mice for histopathologic analysis. Results: Significant levels of both INF-γ and TFN-α were detected within MCMV-infected eyes of normal mice (33 and 141 pg, respectively) and MAIDS-2 mice (50 and 130 pg, respectively) that were resistant to retinitis. However, IFN-γ levels within MCMV-infected eyes decreased thereafter as eyes became more susceptible to MCMV infection and retinitis during the progression of MAIDS, and eventually dropped in MAIDS-12 mice who were highly susceptible to retinitis to a level found in all control eyes (<10 pg). Surprisingly, TNF-α levels did not decrease within MCMV-infected eyes during the progression of MAIDS and actually increased somewhat in MAIDS-12 mice (197 pg). Conclusions: Increased susceptibility to MCMV retinitis during the progression of MAIDS correlated with a progressive decrease in intraocular levels of IFN-γ, a cytokine that suppresses HIV replication in vitro. In contrast, this correlation was not observed for TFN-α, a cytokine that has been associated with active (inductive) replication of HIV during AIDS.
This PDF is available to Subscribers Only