Cytokines in mice treated with amphotericin B-intralipid.
Amphotericin B (AMB) intralipid (IL) admixtures (AMB-IL) are composed of components approved for clinical use and are commercially available at low cost. They are stable and exhibit in-vitro and in-vivo efficacy against Candida infections, as well as resulting in significantly reduced toxicity in comparison with that of conventionally administered amphotericin B. We examined the production of cytokines in uninfected mice treated with AMB or AMB-IL, as evaluated by expression of mRNA corresponding to the cytokines. Expression was measured by intensity of bands in comparison to the intensity of beta-actin control bands, with the latter assigned an arbitrary standard value of 100% and other bands measured in relative percentages. We found that both in naive and compromised mice, AMB treatment caused significantly greater production of the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) than was seen in animals treated with AMB-IL or with another lipid AMB formulation, AmBisome. We hypothesize that the superior tolerance for the AMB-IL admixtures, as compared with conventional AMB, might derive from the reduced expression of the pro-inflammatory cytokines. TNF-alpha and IL-1beta, which mediate many potentially adverse pathophysiological events similar to those seen as side-effects of AMB usage.
Shadkchan
Y
Y
Department of Human Microbiology Sackler School of Medicine, Tel-Aviv University Tel-Aviv, Israel.
Keisari
Y
Y
Segal
E
E
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D000935:Antifungal Agents; D016207:Cytokines; D005217:Fat Emulsions, Intravenous; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B