Nonlinear response of the reticuloendothelial system upon stimulation.

Abstract

Various single reaction variables of the reticuloendothelial system (RES) may often be measured independently of others, but the total defense response of the host arises from a complex, interconnected set of these reactions. It is important, therefore, to study and attempt to understand the overall effects of substances having RES-modifying properties, as well as their specific effects on subsystems. The results reported here demonstrate that the overall response of a modified RES is strongly dose-dependent and that a specific typical response can be identified as characteristic of the entire system. This implies a biologically integrated system. If a wide enough range of doses can be used, an irregular, nonlinear, nonmonotonic curve is always observed. The plotted data generally show two peaks of maximal action which form a W- or M-shaped curve, with the response occurring at lower doses usually being weaker than that occurring at higher doses. The results described here were obtained by using the following experimental models: <i>Ps. aeruginosa, S. typhimurium, </i>Friend virus and <i>PI. berghei </i>infection in mice, Rous sarcoma virus infection in chicks, endotoxin shock in mice and dibenz-pyrene-induced tumors in mice. Modification of the RES was accomplished by using: bacterial lipopolysaccharide, cholesteryl oleate, coenzyme Q<sub>10</sub> and Restim (shark-liver lipid). Additional data published from other laboratories supporting our results are also presented. The characteristics of the described type of dose-response relationship require that multiple dose ranges must be employed in evaluation experiments both to establish efficacy and to design optimum dose schedules for experimental or clinical use of agents modifying the RES.