ALTERATIONS IN THE FUNCTIONS OF THE RETICULOENDOTHELIAL AND PROTEASE-ANTIPROTEASE SYSTEMS AFTER INTRAPERITONEAL INJECTION OF ZYMOSAN IN RATS

Objective: To evaluate alterations in the function of the reticuloendo thelial system (RES) and potential protective effects of pretreatment with the antioxidants: N-acetyl-L-cysteine (NAC) or dimethyl sulphoxid e (DMSO), after intraperitoneal injection of zymosan (0.50 mg/g body w eight) in rats. Design. Experimental study. Setting: University hospit al, Sweden. Animals: 81 male Sprague-Dawley rats. Intervention: Intrap eritoneal injection of either 4 ml saline or zymosan suspension (0.50 mg/g body weight). One hour before the intraperitoneal injection, I mi of saline, or a solution of NAC (150 mg/kg) or DMSO (80 mg/kg) were g iven intravenously. Main outcome measures: Systemic arterial pressure, packed cell volume, concentrations of plasma proteins and plasma prot ease inhibitors, uptake of I-125-labelled Escherichia coli in organs, blood clearance and body uptake rate of radiolabelled E. coli, and blo od flow in organs at 3, 6, and 12 hours after injection. Results: The uptake of radiolabelled E. coli in the liver, spleen and lungs decreas ed significantly from 3 hours onwards after zymosan challenge (p < 0.0 5). Blood clearance and body uptake rate also decreased significantly from 3 hours onwards (p < 0.05), but this did not correlate with the r eduction in organ blood flow. Significant falls in plasma concentratio ns of prekallikrein (p < 0.01) and protease inhibitors (p < 0.05) sugg ested possible contact-phase activation and activation of the kallikre in-kinin and fibrinolytic system. Pretreatment with NAG, and to a less extent DMSO, significantly prevented these alterations in RES functio n. Conclusion: Zymosan induced an impairment in RES function that was not initially associated with a reduction in blood flow. Plasma proteo lytic activity seems to be involved in the impaired RES function. Pret reatment with NAC or DMSO effectively improved RES function.