A single injection of endotoxin derived from Gram negative bacteria caused an increased survival in lethally irradiated animals when given immediately after or 24 hours before irradiation. Mice responded better to the injection before irradiation and hamsters to the injection after irradiation. The effect was associated with a reduction in infection, very pronounced in the case of α-streptococcus or Proteus and still significant in the case of Pseudomonas infection. No beneficial effect was obtained when mice were given three endotoxin injections during 1 week or six injections during 2 weeks prior to irradiation. The beneficial effect is not necessarily associated with the granulocytosis which begins within a few hours after the endotoxin injection, or with the conditions under which nonirradiated animals show an increased resistance to bacterial challenge.
Mice given an intraperitoneal injection of Salmonella typhosa endotoxin 24 hours before irradiation showed an advance in the recovery of granulocytes, platelets and hemoglobin, with the effect on lymphocyte counts relatively small. Differences in bone marrow cellularity and in ability to mobilize granulocytes were particularly striking. Effects of an injection given after irradiation although significant were less pronounced. The induction of hemopoiesis is thought to be responsible for the increase in survival previously observed with this treatment. It is not known whether the action of endotoxin upon the precursor cells is direct or indirect.
The ability of mice to respond to an intraperitoneal injection of Salmonella typhosa endotoxin with increased resistance to experimental Pseudomonas infection was studied over a period of 3 weeks following just sublethal irradiation, with and without lead shielding of the hind legs. In general, the increase in resistance paralleled the ability to mobilize granulocytes. No increase in resistance was observed 3 days after irradiation in the unshielded mice, while in the shielded mice the increase was only slightly less than in nonirradiated mice. In nonirradiated mice given a series of endotoxin injections, increased resistance to the infection persisted in the absence of a granulocytic response. This effect could be abolished by an intervening exposure to sublethal radiation. An intraperitonial injection of zymosan also increased resistance to the infection without producing a granulocytosis. The rapidly developing resistance to infection following an endotoxin injection was transitory and apparently is not responsible for the recently reported increase in survival of lethally irradiated mice.
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