INFLUENCE OF MACROPHAGE-DEPLETION ON HSV-1 KERATITIS IN MICE
D. Bauer, S. Mrzyk, N. van Roojen1 , K.-P. Steuhl, A. Heiligenhaus
HSV-1 induced stromal keratitis is an immune mediated disease. The role of macrophages has not been defined. The influence of a specific depletion of macrophages on the course of HSV-1 keratitis was investigated.
Methods: The cornea of BALB/c was infected with HSV-1 KOS strain (105 PFU). Prior to infection (day -7), several groups of mice (each n=15) were injected with dichloromethylene diphosphonate (CI2MDP)-liposomes: intravenously (iv), subcutaneously at the regional lymph nodes (sc), iv+sc, or subconjunctivally (oc). The severity of epithelial and stromal keratitis was studied clinically. The eyes were analyzed histologically by day 14 p.i..
Results: In the control group, 80% of mice had developed necrotizing stromal keratitis by day 14 p.i. Treatment with CI,MDP-liposomes reduced the incidence and severity of stromal keratitis: sc (72%), iv+sc (50%), oc (50%); iv treatment alone (80%) was ineffective. The histological studies revealed that the corneal inflammatory cell infiltration was reduced by CI2MDP-liposomes injected sc, iv+sc, or oc. The healing of epithelial HSV-1 keratitis was delayed by CI2MDP-liposomes.
Conclusions: The observations suggest that macrophages play an important role in HSV-1 keratitis: 1. by inhibiting the uncontrolled growth of HSV-1 in the eye (epithelial disease); 2. macrophages may contribute to the immunologically mediated tissue destruction of the cornea (stromal disease).
Dept. of Ophthalmology, University Essen, Hufelandstrasse 55, 45122 Essen
1Dept. of Cell Biology 8 Immunology, University Amsterdam, Netherlands. DFG He 1B77/7-1