Possible mechanisms of glucocorticoid--unresponsive pyrexia. Defect in lipocortin 1?

Glucocorticoids have a strong anti-inflammatory action, and are indispensable in the treatment of inflammatory diseases. We had a patient with the Weber-Christian disease having an intractable high fever that did not respond to even a high-dose glucocorticoid therapy, but was responsive to a nonsteroidal antiinflammatory drug. To elucidate possible mechanisms of the glucocorticoid-unresponsive fever, we have investigated the in vitro production of two eicosanoids, prostaglandin (PG)E2 and leukotriene (LT)B4, from the peripheral blood polymorphonuclear leukocytes after stimulation by ionophore A23187. The patient's leukocytes produced much larger amount of PGE2, but the same amount of LTB4, as did those of two control groups. More interestingly, the production of eicosanoids was inhibited by dexamethasone less in the patients than in the controls. Indomethacin suppressed the production of PGE2 both in the patients and in the controls. These results might be relevant in the glucocorticoid-unresponsive pyrexia.