Accelerated host metabolism of L-thyroxine during acute infection: role of the leukocyte and peripheral leukocytosis.

Metabolism of thyroid hormones is accelerated during acute infection in man and in experimental animals. The pathogenetic mechanisms mediating this phenomenon are uncertain, but activated leukocytes of the infected host have been implicated as potentially important sites of hormone degradation. The present studies were conducted in an attempt to assess the in vivo contribution of leukocytes and peripheral leukocytosis to the enhancement of L-thyroxine (T4) clearance seen during infection, and to evaluate further the possible roles of fever and of changes in the extracellular binding of T4. In 10 rhesus monkeys inoculated with virulent yellow fever (YF) virus, peripheral disposal of T4 was significantly accelerated (2-fold) during the febrile phase of the illness. This experimental viral infection was not accompanied by neutrophilic leukocytosis nor by detectable changes in serum free T4 levels, suggesting that neither an increased circulating neutrophil mass nor diminished extracellular binding of T4 contributed appreciably to the increase in metabolism of T4. A pathogenetic role for fever in the enhancement of T4 degradation was not specifically excluded in these infected monkeys. However, the failure of T4 turnover to increase during other febrile infections, such as that which followed inoculation of monkeys with Venezuelan equine encephalitis virus, indicates that the acceleration of peripheral disposal of T4 seen in infection is not a simple concomitant of fever. In monkeys with bacterial sepsis and in those inoculated iv with zymosan particles, T4 turnover was similarly accelerated in the absence of detectable changes in serum free T4 levels, suggesting a pathogenetic role for enhances cellular uptake and metabolism of hormone. However, in these monkeys deiodination of T4 by leukocytes did not appear to account for the increase in T4 disposal. During sepsis and following zymosan administration, T4 turnover was markedly increased in both intact monkeys with a neutrophilic leukocytosis and in those with irradiation-induced neutropenia. Therefore, the cellular sites of increased T4 degradation during infection remain uncertain. Fixed tissue macrophages serve as the major site of clearance of YF virus, circulating bacteria and zymosan particles. Accordingly, a relationship between activation of these phagocytic cells and the acceleration of T4 metabolism seemed possible but was not established by our studies.