Sepsis inhibits synthesis of myofibrillar and sarcoplasmic proteins: modulation by interleukin-1 receptor antagonist.

Abstract

The breakdown of myofibrillar and sarcoplasmic (nonmyofibrillar) proteins are regulated independently in sepsis, however, the factors regulating their synthesis are unknown. In this study, we assessed the effects of sepsis and interleukin-1 receptor antagonist on sarcoplasmic and myofibrillar protein synthesis in gastrocnemius. The rate of sarcoplasmic protein synthesis was 3.5 times that of myofibrillar proteins in control and septic rats. The synthesis of both sarcoplasmic and myofibrillar proteins was diminished proportionately during sepsis (p < .05). Infusion of interleukin-1 receptor antagonist (2 mg.kg.-1.h.-1) prevented the sepsis-induced inhibition of total, sarcoplasmic, and myofibrillar protein synthesis. Changes in the abundance of messenger RNA could not account for the inhibition of protein synthesis observed in sepsis. Furthermore, in vitro translation of messenger RNA isolated from control and septic muscle revealed no major differences. These results suggest the following: 1) the inhibition of total mixed proteins during sepsis is a consequence of reduced synthesis of both myofibrillar and sarcoplasmic proteins; 2) IL-1ra maintains control values of protein synthesis by sparing the reduction in synthesis of both myofibrillar and sarcoplasmic proteins during sepsis; and 3) the abundance of messenger RNA is not a rate-limiting determinant of protein synthesis in muscle from septic rats. An alteration in the translational efficiency of existing mRNA appears to be the major mechanism responsible for the inhibition of protein synthesis during sepsis.