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E. F. Hall, D. M. Reed, D. N. Zacks; Cytokine Profiles in Experimental Rabbit Models of Treated and Untreated Infectious Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2480.
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To investigate the cytokine profiles over time in rabbit models of treated and untreated infectious endophthalmitis.
The right eye of 69 New Zealand white rabbits received an intravitreal injection of either 3.5 X 105 to 4.0 x 105 Staphylococcus epidermidis (SE) (n=36) or 102 Bacillus cereus (BC) (n=33) organisms The left eye of each animal served as a control and received no injection. Eighteen SE and 12 BC injected eyes received treatment at t=24 h with either Vancomycin (V) (1mg/0.1mL) (SE: n=9, BC: n=6) or Vancomycin plus Dexamethasone (VD) (400µg/0.1mL) (SE: n=9, BC: n=6).In the untreated SE group, 3 animals were sacrificed at each of the following time points: 6, 12, 24, 48, 72, and 168 hours. In each of the treated SE groups, 3 animals were sacrificed at each of the following time points: 48, 72, and 96 hours. In the untreated BC group, 3 animals were sacrificed at each of the following time points: 6, 12, 24, 36, and 60 hours (6 animals at 48 hours). In each of the treated BC groups, 3 animals were sacrificed at 48 and 60 hours.Prior to sacrifice, both eyes of each animal were examined for signs of endophthalmitis (photophobia, conjunctival/iris injection, and vitritis) using a standardized grading protocol. Following euthanasia, each eye was enucleated, and vitreous cavity contents of infected (right) and control (left) eyes were individually analyzed for multiple cytokine levels by Quansys Biosystems on their Q-Plex miniaturized sandwich ELISA mouse and human arrays.
Most injected eyes showed clinical signs of endophthalmitis within 24 hours. None of the control eyes showed signs of infection. Clinical inflammatory scores were decreased in all treated animals. In the SE group, IL-1β, Il-2, MIP-1α, and IL-8 were elevated in infected animals, but showed no change or even decreased levels when animals were treated with either V or VD. Conversely, MCP-1 and IFN-γ were not changed in infected animals, but increased in animals treated with V or VD. In the BC group, IL-1β, MIP-1α, IL-8, and IFN-γ were elevated in infected animals, but showed decreased levels when animals were treated with either V or VD.
Staphylococcus epidermidis and Bacillus cereus endophthalmitis each induce a specific cytokine response that is modulated with treatments. These changes in cytokine profiles over time correlate well with the changes in clinical inflammatory scores. Understanding cytokine profiles in infectious endophthalmitis and their modulation may lead to a better understanding of inflammatory mechanisms and to better diagnostic and therapeutic alternatives for patients with infectious endophthalmitis.
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