Effect of fusidic acid on interleukin-1 (IL-1)- and IL-6-induced pancreatic beta-cell functions in rats.
Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs with a steroidal primary structure. Both compounds have been shown to prevent the lymphocyte co-stimulatory activities of the cytokines, interleukin (IL)-1 and IL-6, in a manner similar to that of cyclosporin A. As shown in this paper, fusidin also prevents the inhibitory effect of human recombinant IL-1 beta (rIL-1 beta) and the stimulatory effect of human rIL-6, on glucose-induced insulin production in vitro by normal rat pancreatic islets. The drug also inhibited rIL-1 beta-induced IL-6 production by the islets. Fusidin showed a dose-related effect at pharmacologically relevant concentrations from 3 to 30 micrograms/ml, and the drug was progressively less active when added 1, 4 and 24 h after rIL-1 beta. Electron microscopical studies showed that beta cells cultured for 72 h with rIL-1 beta accumulated less lipid in the presence of fusidin, most probably reflecting the functionally protective effect of the drug. Other characteristic ultrastructural changes induced in beta cells by rIL-1 beta were, however, not altered. It is suggested that fusidin may prove clinically effective as a modulator of IL-1- and IL-6-induced changes in beta-cell functions.
Bendtzen
K
K
Laboratory of Medical Immunology, Rigshospitalet, Copenhagen, Denmark.
Diamant
M
M
Horn
T
T
Pedersen
C
C
Buschard
K
K
D000818:Animals; D002478:Cells, Cultured; D005672:Fusidic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D005672:Fusidic Acid; D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors