Tumor necrosis factor-alpha in macrophages of heart, liver, kidney, and in the pituitary gland

Tumor necrosis factor-alpha (TNF alpha) is an important mediator in bacterial lipopolysaccharide (LPS)-induced fever and shock. New data on TNF alpha-producing macrophages in heart, pituitary gland, kidneys and liver in correlation with TNF alpha plasma levels are reported here. In adult rabbits, core temperature and TNF alpha plasma levels are significantly increased at 3 and 24 h after treatment with LPS. After a delay of 6-12 h, the number of TNF alpha-containing macrophages, determined by immunohistochemistry, increases more than fivefold in all organs investigated. With the exception of the pituitary gland, the increase in cell number is correlated with the degree of cellular injury, indicating the involvement of TNF alpha in LPS-induced organ damage that is accompanied by the synthesis of the cytokine. Cortisol levels also increase for at least 24 h after LPS treatment, show peak values 6 h after interleukin-1 treatment, and are unchanged after TNF alpha treatment, indicating the different effects of these factors on the hypothalamo-hypophyseal-adrenocortical axis. This study provides evidence that macrophageal TNF alpha of multi-organ origin is involved in LPS-induced tissue injury and supports the concept of a systemic inflammatory response syndrome. We also show for the first time that in the anterior lobe of the pituitary gland TNF alpha is a normal constituent in cells producing growth hormone but not ACTH. Moreover, most cells of the intermediate lobe are positive for TNF alpha.