Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis

Abstract

A B S T R A C T The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T4) distribution and metabolism and on serum total and free T4 concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T4 from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T4 disposal. In the infected monkeys, serum total T4 and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T4 were enhanced by 4 h after inoculation of monkeys with either heatkilled or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T4 kinetics could neither be correlated with changes in the binding of T4 in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T4 disappearance was also observed during Escherichia coli and Diplococcus pneumioniae bacteremias. Our findings are Dr. Woeber's present address is the

Metabolism of L-Thyroxine by Phagocytosing Human Leukocytes

“…Our failure to observe an increased proportion of Ts following induction of phagocytosis may have reflected enhanced degradation of the newly-formed T3 in this circumstance. Finally, although its significance with respect to overall thyroid hormone economy has not been directly evaluated, it seems possible that the increased metabolism of T4 by phagocytosing cells may contribute to the accelerated cellular uptake and metabolism of T4 that occur in the host during acute bacterial sepsis (1,21,22).…”

The Response of the Thyroid Gland and Thyroid Hormone Metabolism to Infectious Disease

“…Fractional T4 turnover may be accelerated during pneumococcal infec tion in rats [5], monkeys [8] and man [6] and during other febrile states in monkeys [9] and in man [3,7]. Turnover and peripheral disposal have been shown to be depressed, however, during malarial infection in man [13], Despite a number of technical criticisms and the errors inherent in assuming single compartmental kinetics during infectious disease, these contrary ob servations seem valid.…”

“…Shambaugh and Beisel [5] observed an acceleration in k during pneumococcal septicemia in rats, and D e Rubertis and Woeber [9] also found an increased T4 turnover and disposal rate during Salmonella typhimurium or Escherichia coli sepsis in rhesus monkeys. Sterling and Chodos [3] found elevations in k in five febrile euthyroid patients, four of whom had leukemia, one a urinary tract infection.…”

“…A number of studies have suggested that serum PBI falls during acute infection in rats [5] rabbits [23] and monkeys [8,9] and then rebounds to values greater than those seen during control periods. While some studies have indicated no change [6] or a slight increase [24], most workers have observed modest decreases in PBI during infectious illness in man as well, again often demonstrating a rise to normal limits or greater during recovery [7,13,[20][21][22].…”

“…Conceivably, release of iodine, iodotyrosines, or iodoproteins might occur to a greater extent during infec tion and could be measured in the PBI. Consequently, the more recent studies [8,9,13] which assayed serum T4 by competitive protein binding methods [28] would more specifically reflect changes in levels of hormone in blood. In this regard, the probable validity of the PBI measurement is sup ported by estimates of rates of nonhormonal iodine release [29], which have been shown to be decreased during malarial infection [30], The effects of infectious illness or fever on the concentration of T3 in serum, or of changes in the rate of conversion of T4 to T3 have not yet been reported.…”