Possible alteration of normal mechanisms of endotoxin toxicity in vivo by actinomycin D.
The effect of actinomycin D on the sensitivity of endotoxin-responsive (C3HeB/FeJ) and endotoxin-unresponsive (C3H/HeJ) mice to challenge with purified lipopolysaccharide (LPS) of Escherichia coli strain O55:B5 was examined using an experimental protocol of adoptive transfer of lymphoid cells into lethally irradiated recipients. Earlier results--that in the absence of actinomycin D, the ability of LPS to cause a lethal response in the immunologically chimeric mice reflected the phenotypic response of the donor lymphoid cells--were confirmed. Simultaneous administration of actinomycin D to endotoxin-responsive C3HeB/FeJ mice increased by several orders of magnitude the sensitivity of these mice to the lethal effects of LPS. Determinations of 50% lethal doses in the presence of actinomycin D indicated that immunologic chimeras were sensitive to lethal effects of LPS if either the donor or the recipient phenotype was LPS-responsive. Thus, the mechanism(s) of host response to LPS in the presence of actinomycin D may not be identical to those elicited in untreated mice.
D000818:Animals; D002678:Chimera; D003609:Dactinomycin / Q000494:pharmacology*; D004351:Drug Resistance; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000633:toxicity*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H
D004731:Endotoxins; D008070:Lipopolysaccharides; D003609:Dactinomycin