Modulation of host defense by hydrocortisone in stress doses during endotoxemia
- 89 Downloads
To investigate the effects of low-dose hydrocortisone (HC) on neutrophil respiratory burst, phagocytosis, and elimination of E. coli from blood and tissue under endotoxemic and non-endotoxemic conditions.
Randomized, controlled trial.
Experimental laboratory, university hospital.
Forty-eight female chinchilla rabbits (n=8 in six groups A–F).
In order to quantify the bacterial clearance process, defined numbers [108 colony forming units (CFU)] of Escherichia coli were injected intravenously into all anesthetized rabbits. Group A did not receive further intervention. Group B received bolus administration of HC 1.4 mg/kg and group C 14 mg/kg. Endotoxin (LPS, 40 μg/kg/h) was given to groups D, E, and F. Group E received additional bolus administration of HC 1.4 mg/kg and group F 14 mg/kg. All HC groups (B, C, E, and F) were continuously infused with HC 0.18 mg/kg/h.
Monitored parameters were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, serum lactate and LPS concentrations, as well as nitrite and nitrate levels. Tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.
In controls HC significantly delayed elimination of injected E. coli from the blood (P<0.01). LPS also prolonged bacterial elimination but additional HC did not further delay removal of E. coli from the blood. Under endotoxemia HC depressed respiratory burst, whereas phagocytosis functions remained unaltered. Moreover, bacterial colonization of organs was reduced after HC in the LPS groups. Significance, however, was reached only in the liver (P<0.05). Due to HC, clearance from LPS (P<0.01) and lactate (P<0.05) were improved. Levels of nitrite and nitrate did not differ among the groups.
HC demonstrated immunomodulatory effects even in stress doses. In endotoxemic states use of low-dose HC seems to be favorable, although not in non-septic conditions.
KeywordsHydrocortisone Respiratory burst Phagocytosis Neutrophils Bacterial killing Sepsis
The authors thank Dr. Renate Urbaschek, Birgit Kaschta, and Sylvia Thuy (Institute of Med. Microbiology and Hygiene), Kerstin Salomon, Jutta Schulte, Angelika Tapper, Monika Lehmer (Institute of Anesthesiology), and Jutta Christophel (Center of Med. Research, University Hospital of Mannheim, Germany) for excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (DFG, KO1814/2-1) and the Research Fund of the Faculty of Clinical Medicine Mannheim, University of Heidelberg.
- 3.Briegel J, Forst H, Hellinger H, Haller M (1991) Contribution of cortisol deficiency to septic shock. Lancet 338:507–508Google Scholar
- 5.Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K (1999) Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 27:723–732PubMedGoogle Scholar
- 6.Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low-doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871PubMedGoogle Scholar
- 8.Barnes PJ (1996) Mechanisms of action of glucocorticoids in asthma. Am J Respir Crit Care Med 154:21–27Google Scholar
- 14.Sandys GH (1960) A new method of preventing swarming of Proteus sp. with a description of a new medium suitable for use in routine laboratory practice. J Med Lab Technol 17:224–233Google Scholar
- 16.Green LC, Wagner DA, Glogowski J (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Annal Biochem 126:131–138Google Scholar
- 19.Vicente-Manzanares M, Sancho D, Yanez-Mo M, Sanchez-Madrid F (2002) The leukocyte cytoskeleton in cell migration and immune interactions. Int Rev Cytol. 216:233–289Google Scholar
- 23.Pfeiffer L, Ehrhardt N, Kretzschmar M, Urbaschek R, Schubert K, Schirrmeister W (1996) Endotoxinämie und Multiorganversagen nach Polytrauma. Anaesthesiol Reanimat 21:91–96Google Scholar
- 28.Walker BR, Williams BC (1992) Corticosteroids and vascular tone: mapping the messenger maze. Clin Sci (Lond) 82:597–605Google Scholar