Open Access In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin

Background: Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. Results: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentrationdepended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, whil