Pyrogenic and Inflammatory Properties of Certain Bile Acids in Man*

Abstract

This is a report on the pyrogenic and inflammatory properties of certain bile acids in man. The study was prompted by the structural similarity between these acidic steroids and the pyrogenic neutral steroids described previously (2-7). In addition, it seemed important to establish whether the large quantities of steroid acids formed during the metabolism of cholesterol could serve as a source of endogenous compounds having fever-producing action in man. METHODS AND RESULTSNineteen bile acids and derivatives were examined for fever-producing activity after their intramuscular administration to adult volunteer hospital patients. Lithocholic acid was repeatedly recrystallized to insure purity. The glycine, taurine, and acetyl derivatives of lithocholic acid were synthesized and purified in these laboratories; the other compounds were obtained commercially and used without additional purification. All bile acids were dissolved in propylene glycol, in concentrations of 12.5 and 25.0 mg per ml, and because of their acidity these solutions were neutralized with dilute base. The general details of the study, including precautions taken to exclude bacterial pyrogen contamination, were similar to those described in a previous report (3). The compounds examined, together with the incidence of pyrogenic responses which followed their injection, are listed below.

Studies on steroid fever II. Pyrogenic and anti-pyrogenic activity in vitro of some endogenous steroids of man

“…A saturated buffer solution of lithocholic acid was clearly effective in stimulating release of leukocyte pyrogen, whereas deoxycholic acid did not induce pyrogen release (see Table I). Similar pyrogenic properties of these compounds have been reported in vivo (12).…”

“…Certain bile acids, which have structures similar to those of the steroids discussed above, have been reported to be pyrogenic in man (12). A saturated buffer solution of lithocholic acid was clearly effective in stimulating release of leukocyte pyrogen, whereas deoxycholic acid did not induce pyrogen release (see Table I).…”

“…Both C-19 (3)(4)(5)10) and C-21 (4, 5, 11) steroids, as well as certain bile acids (12), have been studied. It seemed of interest to examine the action of some of these steroids on leukocytes in vitro, to determine whether similar structural features would also be required for pyrogenic activity in this system.…”

Effect of sodium taurolithocholate on bile flow and bile acid excretion

“…Although the physical properties of sodium taurolithocholate can explain the initial events in cholestasis, consideration should be given to the marked hemolytic and inflammatory properties that occur (11,28). The mechanisms for these effects are not precisely known, but presumably the configuration of the molecule disrupts the membrane leading to liberation of hemoglobin from erythrocytes and inflammation in tissues.…”

Inflammatory Myofibroblastic Tumor of the Liver Following Renal Transplantation

“…These findings were compatible with IMT. 10,11 At present, the exact pathogenesis of IMT is not so clear; several theories have been proposed for the possible etiology of IMT. Recently, cases of inflammatory pseudotumor in association with transplantation have been successively reported although it is a rare condition.…”