The pathophysiologic roles of interleukin-6 in human disease

Interleukin-6, an inflammatory cytokine, is characterized by

pleiotropy and redundancy of action. Apart from its

hematologic, immune, and hepatic effects, it has many

endocrine and metabolic actions. Specifically, it is a potent

stimulator of the hypothalamic-pituitary-adrenal axis and is

under the tonic negative control of glucocorticoids. It

acutely stimulates the secretion of growth hormone, inhibits

thyroid-stimulating hormone secretion, and decreases serum

lipid concentrations. Furthermore, it is secreted during

stress and is positively controlled by catecholamines.

Administration of interleukin-6 results in fever, anorexia,

and fatigue. Elevated levels of circulating interleukin-6 have

been seen in the steroid withdrawal syndrome and in the severe

inflammatory, infectious, and traumatic states potentially

associated with the inappropriate secretion of vasopressin.

Levels of circulating interleukin-6 are also elevated in

several inflammatory diseases, such as rheumatoid arthritis.

Interleukin-6 is negatively controlled by estrogens and

androgens, and it plays a central role in the pathogenesis of

the osteoporosis seen in conditions characterized by increased

bone resorption, such as sex-steroid deficiency and

hyperparathyroidism. Overproduction of interleukin-6 may

contribute to illness during aging and chronic stress.

Finally, administration of recombinant human interleukin-6 may

serve as a stimulation test for the integrity of the

hypothalamic-pituitary-adrenal axis.

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