On "Down-Regulation of Albumin Synthesis in the Rat by Human Recombinant Interleukin-1β or Turpentine and the Response to Nutrients"

treated with IL-1 (3 or turpentine. In contrast, the IV feeding stimulated albumin synthesis in control rats only, whereas in rats with an inflammatory response induced by IIrl~3 or turpentine, albumin synthesis was not influenced by the feeding regimen. The study confirms a number of previous reports of reduced synthesis of albumin (a dnegatived acute phase protein) and increased total liver protein synthesis during the acute phase response. Thus, in this respect, the paper does not provide new information. Other authors have found evidence that the differential effect of inflammation on the synthesis of acute phase proteins and albumin is regulated at the transcriptional level as evidenced by increased concentrations of mRNA for fibrinogen and other acute phase proteins and reduced levels of albumin mRNA1 and one has to assume that similar molecular regulation occurred in the experiments described by Ballmer et al. It would have been of great interest to see liver tissue levels of albumin mRNA and mRNA for one or several of the acute phase proteins, presumably accounting for a substantial part of total liver protein synthesis in the current experimental model. Although cytokine levels were not measured in the present paper, other reports suggest that IIr6 is probably the most important mediator of the acute phase response in the liver. It is likely that the effect of IL-1 (3 and turpentine observed in the current study was at least partly mediated by IIr6, possibly with glucocorticoids acting as a cofactor. Measurements of circulating and tissue levels of IL6 and other proinflammatory cytokines would be important to better defme mediators of the acute phase response in the experimental model used by the authors. Even more importantly, blockade of putative mediators with specific antibodies and/or receptor antagonists would help dissect the role of various cytokines. From a clinical standpoint, the most important part of the study addresses the role of nutrition in the regulation of the inflammatory response. Total liver protein synthesis, already increased by IL-1 (3 or turpentine, was further stimulated by a short-term IV feeding. In contrast, the suppressed albumin synthesis was not affected by the nutritional regimen. It would have been interesting to see the effect of a more extended period of IV nutritional support; that might have helped us decide whether the down-regulated albumin synthesis is resistant to nutritional intervention during the inflammatory response. From a teleological standpoint, it may be speculated that the reduced production of albumin is part of the reprioritization of hepatic protein synthesis described approximately 10 years ago.’ If so, it makes sense that the inhibited albumin synthesis is resistant to therapeutic interventions so that the liver can continue to make acute phase proteins at a high rate. Although mediators and mechanisms of the acute phase response were not explored, the study by Ballmer and colleagues is important because it addresses a clinically significant phenomenon. A well-maintained hepatic protein synthesis during sepsis and inflammation is important for host defense and, ultimately, survival.¢ 4