Patients with severe head injury are hypermetabolic and hypercatabolic. Postulated mechanisms for these metabolic disturbances include increased levels of catecholamines and increased levels of cortisol, glucagon and other regulatory hormones. Interleukin-1 (IL-1) is a monokine which is released from a variety of monocyte/macrophage cells within the body. IL-1 plays a major role in modulation of the immune system and in mediation of several aspects of the acute phase response. The nonimmunologic role of IL-1 is the focus of this grant. IL-1 has been shown to mediate fever, cause synthesis of acute phase reactants, induce neutrophilia, produce muscle breakdown, and cause alterations and redistribution of minerals such as zinc. We recently described marked alterations of zinc metabolism in head trauma patients, which we suggest are mediated by interleukin-1 release. Preliminary data from our laboratory revealed that 8/8 patients with severe head injury had elevated ventricular fluid IL-1 activity; whereas, no control patients undergoing myelograms had detectable cerebral spinal fluid IL-1 activity. Similarly, in 7 other severe head injury patients studied, the mean admission serum IL-1 activity index was significantly increased, and this index decreased toward normal during the course of hospitalization. We propose to measure IL-1 activity in severe head injured patients with or without extracranial trauma. We will determine whether IL-1 activity and/or the additin of multiple trauma correlates with factors such as mineral levels, indicators of muscle catabolism, and suggested mediators of the hypermetabolic/hypercatabolic state such as catecholamines and endorphins. In vitro studies will evaluate the role of various hypermetabolic/hypercatabolic mediators such as epinephrine, norepinephrine and ACTH on release of IL-1 from human monocyte and astrocyte cell lines. Studies in animals will evaluate the effect of IL-1 injection on release of hormones such as ACTH, corticosterone and catecholamines. Lastly, we will determine whether there is detectable proteolysis inducing factor (a cleavage product of IL-1) in the serum of head trauma patients that causes in vitro muscle breakdown. This series of studies will provide initial information concerning the role of interleukin-1 in head injured patients and may provide new insight in the treatments of the altered metabolic state regularly observed in these patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022712-02
Application #
3405524
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Ott, M; Schmidt, J; Young, B et al. (1994) Nutritional and metabolic variables correlate with amino acid forearm flux in patients with severe head injury. Crit Care Med 22:393-8
Hennig, B; Wang, Y; Ramasamy, S et al. (1992) Zinc deficiency alters barrier function of cultured porcine endothelial cells. J Nutr 122:1242-7
Young, B; Ott, L; Yingling, B et al. (1992) Nutrition and brain injury. J Neurotrauma 9 Suppl 1:S375-83
Boosalis, M G; Solem, L D; Cerra, F B et al. (1991) Increased urinary zinc excretion after thermal injury. J Lab Clin Med 118:538-45
Ott, L; Young, B; Phillips, R et al. (1991) Altered gastric emptying in the head-injured patient: relationship to feeding intolerance. J Neurosurg 74:738-42
McClain, C; Cohen, D; Phillips, R et al. (1991) Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury. J Lab Clin Med 118:225-31
Ott, L; Young, B; Phillips, R et al. (1990) Brain injury and nutrition. Nutr Clin Pract 5:68-73
Ott, L; McClain, C; Young, B (1989) Nutrition and severe brain injury. Nutrition 5:75-9
Kolpek, J H; Ott, L G; Record, K E et al. (1989) Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-treated severe head trauma patients. JPEN J Parenter Enteral Nutr 13:277-80
Goldblum, S E; Hennig, B; Jay, M et al. (1989) Tumor necrosis factor alpha-induced pulmonary vascular endothelial injury. Infect Immun 57:1218-26

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