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WOEBER, DeRUBERTIS
Accelerated cellular uptake and metabolism of L-thyroxine during acute Salmonella typhimurium sepsis.DeRubertis FR, Woeber KA. J Clin Invest. 1973 Jan;52(1):78-87.
"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 consistent with a primary increase in the cellular uptake and metabolism of T4 during bacterial sepsis, possibly related to phagocytic cell function in the host."
Metabolism of L-thyroxine by phagocytosing human leukocytes.Woeber KA, Ingbar SH. J Clin Invest. 1973 Aug;52(8):1796-803.
"Intact normal human leukocytes deiodinated L-thyroxine (T4) with the generation of inorganic iodide, chromatographically immobile origin material, and small quantities of L-triiodothyronine (T3). When phagocytosis was induced in the leukocytes through the addition of zymosan particles that had been opsonized by coating with plasma, T4-deiodination was greatly stimulated. In addition to the stimulation of T4-deiodination, the accumulation by the leukocytes of undegraded T4 was increased. Anoxia, which has previously been shown not to interfere with phagocytosis, did not prevent the increased cellular accumulation of T4 that phagocytosis induced, but virtually abolished T4-deiodination. On the other hand, calcium, which has previously been shown to be required for optimal phagocytosis, was required for the increase in both the cellular accumulation and deiodination of T4 that phagocytosis induced. Phospholipase-C, which has previously been shown to induce a metabolic burst that mimics that induced by phagocytosis, did not increase the cellular accumulation or deiodination of T4. On the other hand, colchicine, which has previously been shown to depress the metabolic burst that accompanies phagocytosis, did not prevent the increase in either the cellular accumulation or deiodination of T4 that phagocytosis induced. Thus, increased accumulation of T4 by the leukocytes during phagocytosis appears to be the primary factor responsible for the stimulation of deiodination that phagocytosis induces. The increased accumulation of T4 did not appear to be owing to engulfment of suspending medium surrounding the particles or to binding of T4 to the particles themselves. In addition to the enhanced cellular accumulation, other factors related to the metabolic burst that accompanies phagocytosis might also be involved in the stimulation of T4-deiodination. In leukocytes from two patients with chronic granulomatous disease, a disorder in which phagocytosis appears to occur normally but in which the metabolic burst and attendant increase in hydrogen peroxide generation do not occur, stimulation of T4-deiodination was either greatly diminished or totally lacking. In myeloperoxidase-deficient leukocytes, on the other hand, stimulation of T4-deiodination was at least as great as that in normal cells. Thus, we conclude that the primary factor responsible for the increased deiodination of T4 that phagocytosis induces is the enhanced cellular uptake of hormone. The increased generation of hydrogen peroxide that accompanies phagocytosis may be necessary for the enhanced deiodination of the accumulated T4, but the latter reaction does not require the mediation of myeloperoxidase."
Evidence for enhanced cellular uptake and binding of thyroxine in vivo during acute infection with Diplococcus pneumoniae.DeRubertis FR, Woeber KA. J Clin Invest. 1972 Apr;51(4):788-95.
"Previous work has demonstrated that acute pneumococcal infections in man and in the rhesus monkey are accompanied by accelerated metabolic disposal of L-thyroxine (T4). In order to study the influence of acute pneumococcal infection on the kinetics of hormone distribution, the early cellular uptake of T4 (CT4), reflecting the net effect of plasma and cellular binding factors, was assessed in rhesus monkeys....Thus, in the infected monkeys CT4 and% FT4 were not significantly correlated. The increased CT4 in the infected monkeys could not be ascribed to an increase in vascular permeability and did not correlate with the magnitude of fever. Although the increased CT4 could not be accounted for by increased hepatic or renal uptake of hormone, hepatic and renal T4 spaces were increased, results consistent with increased binding by these tissues. Our data indicate that the cellular uptake of T4 is increased early in acute pneumococcal infection and suggest that this results from a primary enhancement of cell-associated binding factors for T4."
Alterations in thyroid hormone economy during acute infection with Diplococcus pneumoniae in the rhesus monkey.Woeber KA. J Clin Invest. 1971 Feb;50(2):378-87.
"In order to study the alterations in thyroid hormone economy that accompany an acute bacterial infection, rhesus monkeys were inoculated i.v. with a virulent Diplococcus pneumoniae culture containing approximately 108 organisms per dose. This was found to produce a well-defined febrile illness followed in most instances by spontaneous recovery, thereby permitting sequential observations to be made during progression from the healthy state through acute infection into convalescence. During the acute febrile period of the infection, the clearance of both exogenously labeled L-thyroxine (T4) and 3,3,5-triiodo-L-thyronine (T3) from their peripheral pools was accelerated. This alteration was often evident by 8 hr after inoculation with the virulent culture and could not be ascribed to a decrease in extracellular binding. Despite the accelerated hormonal clearance, the concentrations of both endogenously labeled thyroid hormone and stable T4 in the sera of the surviving monkeys remained essentially unchanged or increased, indicating that hormonal secretion must have increased during this period. During the convalescent period, hormonal clearance was similar to preinfection control values. Leukocytes isolated from blood obtained 6 hr after inoculation with the virulent culture displayed enhanced T4-deiodinative activity."
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