Metabolic responses to interleukin-1: centrally and peripherally mediated.

Abstract

The purpose of this study was to differentiate between the catabolic effects of interleukin-1 (IL-1) when infused into the central nervous system or into the periphery. After injury and infection, IL-1 has been found in the central nervous system. Chronic intracerebrovascular infusion of IL-1 produces protein catabolism, anorexia, and fever. However, IL-1 may act directly on liver and bone marrow to elicit metabolic responses. Although IL-1 is thought to be involved in a number of metabolic responses associated with injury-inflammation, the sites of action are unclear. Rats were implanted with chronic infusion pumps and received diluent or three doses of IL-1 infused subcutaneously for 6 days, and a variety of response variables were measured. In a second study, doses were adjusted so that similar systemic catabolic responses were obtained from peripheral and intracerebroventricular infusion of IL-1. The acute-phase responses then were compared in the two groups of animals receiving IL-1 by different routes. Subcutaneously infused IL-1 elicited catabolic responses in a dose-response manner. Similar catabolic responses were achieved by infusing one tenth of the dose of IL-1 given subcutaneously into the central nervous system. Although similar systemic responses (protein catabolism, anorexia, fever, and weight loss) were observed with both routes of infusion, the subcutaneous infusion produced a much greater lymphocytosis, elevation in acute-phase reactants, and fall in serum iron and albumin. The IL-1 appears to have different effects depending on the site of production and site of action. Regionalization of signal proteins such as IL-1 should be taken into consideration when devising specific anticytokine treatment strategies.