Abstract

P 224

Protective role of pro-inflammatory mediators in experimental and clinical ocular toxoplasmosis

Javier Prada1, Thanh Ngo-Tu2
1Department of Ophthalmology and Biomedical Research Center, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Berlin, 2Department of Ophthalmology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Microbiology, University of Hanoi, Hanoi, Vietnam, Hanoi, Vietnam

Objective
The role of pro-inflammatory mediators in ocular toxoplasmosis remains unclear and needs to be further elucidated. In this work, pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as the accumulation of nitric oxides (NO), were studied in relation to their possible protective roles during ocular toxoplasmosis.
Methods
The cytokines IL-6 and TNF-alpha were routinely analysed either by available ELISA-kits, or by the B9 and WEHI164 bioassays, respectively, and NO were evaluated as the end concentration of nitrite by a compensated Griess reaction. Statistical analysis was performed by using the t-Student test and the Pearson’s correlation coefficient (PCC).
Results
In murine models, mRNA transcripts for pro-inflammatory mediators, such as IL-6, TNF-alpha and inducible NO-synthase (iNOS), were significantly increased during ocular toxoplasmosis. Moreover, mice treated with TNF-alpha were not protected against lethal challenges with Toxoplasma parasites, but mice treated with anti-TNF-alpha antibodies showed increases in trophozoite numbers and transient signs of illness. Inhibition of NO production after treatment with L-NAME in T. gondii infected mice resulted in a marked increase in the symptoms of ocular inflammation. In the clinical situation, increased levels of IL-6, TNF-alpha and NO were often found to correspond with critical events during ocular toxoplasmosis, such as extended conjunctivitis, vitreous turbidity and/or temporary blindness. As observed in the murine models, the best correlation in the clinical situation was observed between TNF-alpha and NO (PCC: 0.4), whereas IL-6 presented PCCs of 0.3 with TNF-alpha and with NO.
Conclusions
As in the murine models, the significantly increased levels of IL-6, TNF-alpha and NO in the clinical situation may also represent and further confirm a protective role for the host by controlling the number of Toxoplasma parasites and the development of ocular complications.

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