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.