LPS-caused secretion of corticosterone is mediated by histamine through histidine decarboxylase.

Escherichia coli lipopolysaccharide (LPS) induced strong time- and dose-dependent secretion of corticosterone (CS) in C3H/HeN mice. In contrast, C3H/HeJ mice were very insensitive to LPS; 100,000 times more LPS was required with C3H/HeJ mice for producing a similar degree of CS secretion as that of C3H/HeN mice. However, C3H/HeJ mice could efficiently respond to other types of stressors, immobilization stress or injection of histamine, a possible mediator of LPS-induced CS secretion (28), leading to a striking increase in the serum levels of CS. Adoptive transfer of spleen cells from C3H/HeN mice converted x-irradiated C3H/HeJ mice to the donor phenotype. Injection of LPS produced a large increase in the activity of histidine decarboxylase (EC 4.1.1.22) in the spleen, lung, and liver of C3H/HeN mice, whereas C3H/HeJ mice were far less responsive. Transfer of spleen cells from the C3H/HeN mice made C3H/HeJ mice sensitive to LPS, leading to an increase in histidine decarboxylase activity in the spleen. There was a statistically significant relationship between the activity of splenic histidine decarboxylase and the serum levels of CS. These results suggest that the LPS-induced secretion of CS is mediated by histamine through induction of histidine decarboxylase in the spleen, lung, and liver. This may be significant in relation to the host-defense mechanism against endotoxemia.