Kinetic estimation of discrepancy between rats and humans regarding the immunological response to MGN-3/Biobran
Yeh Chen, Hui-Er Wang, Jing-Gung Chung, Robert Y. Peng
The interaction of MGN-3/Biobran in vivo in activating immune response is quite complicated and different between the rats and human. We analyze the major routes of this interaction kinetically and a cytokine mediated model (CMM) is developed to evaluate such a crucial discrepancy between the two biological systems. Rats responded with a kinetic order 1/3, while that of human was 1/24 regarding both MGN-/Biobran and INF-, compared to the predicted value 1/2. As well known, a higher reaction order implicates the more complicate reaction among the reactants. Alternatively, the Monod model gave values of Ks 1.43 and 2.44 mg/kg, and those of Vmax 32.36 and 227.27%/day respectively for rats and human. Apparently, the immunological response of rats was more complicate than human in view of MGN-3/Biobran therapy. We conclude that the discrepancy in the immuno-response between rat and human can reach 3000 folds due to the inter-species variation. We suggest that such differences should be taken into account when using mice or rats as preclinical models of human disease.