Nonantibiotic effects of macrolide antibiotics of the oleandomycin-erythromycin group with special reference to their "steroid-sparing" effects

Certain macrolide antibiotics, such as troleandomycin (TAO), oleandomycin, and erythromycin estolate (Ilosone), can lower the maintenance dose of glucocorticoids required by severely asthmatic patients. These effects were postulated to be caused by an as yet undefined steroid-sparing effect. In this study, TAO in combination with methylprednisolone, when compared with methylprednisolone alone, was demonstrated to significantly increase liver glycogen deposition in adrenalectomized mice, intact mice, and adrenalectomized rats; protect histamine-sensitized mice following beta adrenergic blockade or adrenalectomy; further decrease the steroid-lowered glucose tolerance of mice and significantly increase the plasma corticosteroid levels in rats. TAO alone did not have these effects. TAO plus betamethasone, and erythromycin estolate plus methylprednisolone also increased liver glycogen deposition. However, TAO did not appear to potentiate the effects of hydrocortisone. Erythromycin stearate and to a lesser degree erythromycin ethylsuccinate when combined with methylprednisolone also decreased histamine lethality in mice. Leucomycin and tetracycline did not enhance the effects of methylprednisolone. TAO, alone or with methylprednisolone, did not alter serum glutamic oxaloacetic transaminase (SGOT) levels in rats. Thus, TAO and some other macrolides did not exert their effects on corticosteroids as antimicrobial agents, adrenocorticotropic hormone (ACTH)-like compounds, or quasisteroids, but as steroid-sparing agents by some undefined mechanism.