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

Abstract

Tumor necrosis factor-alpha (TNFalpha) is an important mediator in bacterial lipopolysaccharide (LPS)-induced fever and shock. New data on TNFalpha-producing macrophages in heart, pituitary gland, kidneys and liver in correlation with TNFalpha plasma levels are reported here. In adult rabbits, core temperature and TNFalpha plasma levels are significantly increased at 3 and 24 h after treatment with LPS. After a delay of 6-12 h, the number of TNFalpha-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 TNFalpha 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 TNFalpha treatment, indicating the different effects of these factors on the hypothalamo-hypophyseal-adrenocortical axis. This study provides evidence that macrophageal TNFalpha 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 TNFalpha is a normal constituent in cells producing growth hormone but not ACTH. Moreover, most cells of the intermediate lobe are positive for TNFalpha.

Increased apoptosis of lactotrophs in streptozotocin-induced diabetic rats is followed by increased proliferation

“…In the pituitary, TNF-a is produced by macrophages, as well as by somatotrophs, while lactotrophs do not appear to synthesize this cytokine (Arras et al 1996). Pituitary TNF-a levels were not increased until after 8 weeks of diabetes, and hence, cannot account for the increase in caspase-8 activation at 4 weeks, although it is possible that the second rise in caspase-8 activation at 8 weeks could be related to the increase in local TNF-a.…”

The Prophylactic Effects of Natural Water-Soluble Antioxidant from Spinach and Apocynin in a Rabbit Model of Lipopolysaccharide-Induced Endotoxemia

“…When exposed to sepsis, the corticosterone-producing cells are known to exhibit an enhanced release of hormones, an adrenocorticotropic hormone (ACTH)-regulated activity. Rabbits exposed to a single iv dose of 1 J,Lg/kg LPS showed an increase in the serum cortisol level 24 hours after LPS administration (3). Injections of TNFa and IL-1, respectively, were associated with a late increase in the cortisol with TNFa and an early, short-duration increase in cortisol with IL-1 injection.…”

“…Sensitivity to LPS varies among different species of animals, eg, the rat is reported to be less sensitive than the rabbit (15,59). Injection of rabbits with LPS is reported to lead to endotoxemia accompanied with fever, disseminated intravascular coagulation, and multiple organ injury (3).…”

TNF-α in the cardiovascular system: from physiology to therapy

“…[89][90][91] The presence of TNF-α protein and transcripts is usually restricted to microvessels in the normal heart. 92 However, human cardiac myocytes express functional TNFR1 and respond to TNF-α.…”