title: Differential effects of hemorrhage and LPS on tissue TNF-alpha, IL-1 and associate neuro-hormonal and opioid alterations.
abstract: LPS administration and hemorrhage are frequently used models for the in vivo study of the stress response. Both challenges stimulate cytokine production as well as activate opiate and neuro-endocrine pathways; which in turn modulate the inflammatory process. Differences in the magnitude and tissue specificity of the proinflammatory cytokine and neuro-hormonal responses to these stressors are not well established. We contrasted the tissue specificity and magnitude of the increase in circulating and tissue cytokine (TNF-alpha, IL-1alpha and IL-1beta) content in response to either fixed-pressure hemorrhage (approximately 40 mm Hg) followed by fluid resuscitation (HEM) or lipopolysaccharide (LPS; 100 microg/100 g BW) administration. LPS and HEM elevated circulating levels of TNF-alpha, while neither stress altered circulating IL-1-alpha and IL-beta. LPS-induced increases in TNF-alpha content were greater than those elicited by HEM in all tissues studied except for the lung, where both stressors produced similar increases. Tissue (lung, spleen and heart) content of IL-1alpha was increased by HEM but was not affected by LPS. Tissue (lung, spleen, and heart) content of IL-1beta was increased by LPS but was not affected by HEM. HEM produced greater increases than LPS in epinephrine (16- vs. 4-fold) and norepinephrine (4-fold vs. 60%) levels and similar elevations in beta-endorphin. LPS produced greater elevation in corticosterone levels (2-fold) than HEM (50%). These results suggest differential tissue cytokine modulation to HEM and LPS, both with respect to target tissue and cytokine type. The hormonal milieu to HEM is characterized by marked catecholaminergic and moderate glucocorticoid while that of LPS is characterized by marked glucocorticoid with moderate catecholaminergic influence.
authors.affiliation: Department of Physiology, LSUMC, New Orleans, LA 70112, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Molina
authors.forename: N N
authors.initials: NN
authors.lastname: Abumrad
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D006470:Hemorrhage / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009294:Narcotics / Q000097:blood*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D013312:Stress, Physiological / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*; D001615:beta-Endorphin / Q000097:blood
chemical_list: D002395:Catecholamines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009294:Narcotics; D014409:Tumor Necrosis Factor-alpha; D001615:beta-Endorphin; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine