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Genetic Control of Host Responses to Endotoxin

Two pathophysiological effects of endotoxin in mice have been shown to be under the major influence of polygenic inheritance. The first, endotoxemia, was measured by LD50 assays on hybrids and backcross hybrids of the resistant C3H/HeJ and the susceptible A/HJe strains. The LD50 values of the F1 hybrids and the backcross hybrids were intermediate between the respective parental types. The second effect, the intraperitoneal extravascular leukocyte response to small doses of endotoxin, also was found to follow characteristic patterns of polygenic inheritance. As estimated from an analysis of the variance of mice of the F1 and F2 generations, the degree of genetic determination is approximately 54% for the neutrophil response and 82% for the monuclear response.