Pilotstudie 08.01

Background
We have found that jeopardized (tissue)cells and extra cellular matrix bind secretory phospholipase A2 (sPLA2), facilitating binding of C-reactive protein (CRP) which in the end binds and activates complement. This pro-inflammatory cascade then induces additional tissue destruction in time, even if the primary causative pathological condition has been terminated. In burn patients activation of complement has been found in serum in numerous  studies, although until now, complement, nor the other inflammatory mediators as mentioned above, have been analyzed locally in burn wounds. We recently found that in burn wounds sPLA2, CRP and complement are present locally at least up to 4 weeks (we didn't study wounds beyond that time point). Interestingly the anti-inflammatory mediator Clusterin is positive in the wound 1 day post-burn, but than declines rapidly.

Objective(s)
We hypothesize that activation of the pro-inflammatory pathway: secretory phospholipase A2 (sPLA2) / C-reactive protein (CRP) / complement and reduction of the endogenous  anti-inflammatory mediator Clusterin, results in a continuous local active inflammation in burn wounds which enlarge/deepens the wound and prevents normal wound regeneration.

Methods
1) Analysis of inflammatory mediators in burn wounds and in blood in time. Burn wounds will be induced in rats at different time points. Rats will then be sacrificed. sPLA2, CRP, complement and Clusterin will be measured at a tissue level and in blood.

2) Effect of inhibition of inflammatory mediators. The effect of inhibition of the above mentioned inflammatory mediators in burn wounds will be tested in the rat model.

Anticipated results
New therapy to treat burn patients: inhibition of the acute inflammatory response, preventing additional tissue damage in time and propagating normal tissue regeneration.