SEPSIS INHIBITS SYNTHESIS OF MYOFIBRILLAR AND SARCOPLASMIC PROTEINS -MODULATION BY INTERLEUKIN-1 RECEPTOR ANTAGONIST

The breakdown of myofibrillar and sarcoplasmic (nonmyofibrillar) prote ins are regulated independently in sepsis, however, the factors regula ting their synthesis are unknown. In this study, we assessed the effec ts of sepsis and interleukin-l receptor antagonist on sarcoplasmic and myofibrillar protein synthesis in gastrocnemius. The rate of sarcopla smic protein synthesis was 3.5 times that of myofibrillar proteins in control and septic rats. The synthesis of both sarcoplasmic and myofib rillar 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, a nd myofibrillar protein synthesis. Changes in the abundance of messeng er RNA could not account for the inhibition of protein synthesis obser ved in sepsis. Furthermore, in vitro translation of messenger RNA isol ated from control and septic muscle revealed no major differences. The se results suggest the following: 1) the inhibition of total mixed pro teins during sepsis is a consequence of reduced synthesis of both myof ibrillar and sarcoplasmic proteins; 2) IL-l ra maintains control value s of protein synthesis by sparing the reduction in synthesis of both m yofibrillar and sarcoplasmic proteins during sepsis; and 3) the abunda nce of messenger RNA is not a rate-limiting determinant of protein syn thesis in muscle from septic rats. An alteration in the translational efficiency of existing mRNA appears to be the major mechanism responsi ble for the inhibition of protein synthesis during sepsis.