Immunoactivation and altered intercellular communication mediate the pathophysiology of spinal cord injury

Pharmacotherapy

Volumn 25, Issue 2, 2005, Pages 145-156

  Segal, Jack L ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b HARBOR UCLA MEDICAL CENTER   (United States)

Author keywords

Autonomic failure; Cytokines; ICAMs; Immunology; Pathophysiology; Spinal cord injury; Tetraplegia

Indexed keywords

CYTOKINE;

ADULT RESPIRATORY DISTRESS SYNDROME; AMYLOIDOSIS; ANEMIA; AUTONOMIC DYSFUNCTION; AXONAL INJURY; CALCIFICATION; CARBOHYDRATE INTOLERANCE; CELL COMMUNICATION; CELL PROTECTION; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASE; COMORBIDITY; HOMEOSTASIS; HUMAN; IMMUNOREACTIVITY; IMMUNOREGULATION; LIPID METABOLISM; LONGEVITY; MEDICAL LITERATURE; MEDICAL RESEARCH; METABOLIC DISORDER; MORBIDITY; MORTALITY; NEUROENDOCRINE SYSTEM; NEUROLOGIC DISEASE; NONHUMAN; OSTEOLYSIS; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; QUALITY OF LIFE; RESPIRATORY FUNCTION; REVIEW; SENSORIMOTOR FUNCTION; SPINAL CORD INJURY; THERMOREGULATION;

BIOTRANSFORMATION; BODY COMPOSITION; CELL ADHESION MOLECULES; COMORBIDITY; CYTOKINES; HUMANS; SPINAL CORD INJURIES;

EID: 13544272667     PISSN: 02770008     EISSN: None     Source Type: Journal    
DOI: 10.1592/phco.25.2.145.56958     Document Type: Review

References (165)

1. Claus-Walker J, Halstead LS. Metabolic and endocrine changes in spinal cord injury (4-part series). Arch Phys Med Rehabil 1981-1982;62-3:569-80, 595-601, 628-38.
2. Segal JL, Brunnemann SR, Gordon SK, Eltorai IM. Decreased theophylline bioavailability and impaired gastric emptying in spinal cord injury. Curr Ther Res Clin Exp 1985;38(6):831-46.
3. Segal JL, Rosenzweig IB. Therapeutic drug monitoring and treatment of spinal cord injury. Ther Drug Monit Toxicol 2000;21(2):37-51.
4. Slack RS, Shucart W. Respiratory dysfunction associated with traumatic injury to the central nervous system. Clin Chest Med 1994;15(4):739-49.
5. Bunten DC, Warner AL, Brunnemann SR, Segal JL. Heart rate variability is altered following spinal cord injury. Clin Auton Res 1998;8(6):329-34.
6. Segal JL. Clinical pharmacology in spinal cord injury. In: Young RR, Woolsey RM, eds. Diagnosis and management of disorders of the spinal cord. New York: WB Saunders Co., 1995:414-38.
7. Richardson SJ, Segal JL. Spinal cord injury: the role of pharmacokinetics in optimizing drug therapy. In: Lin VW, ed. Spinal cord medicine: principles and practice. New York: Demos Medical Publishing, Inc., 2002:247-56.
8. Segal JL, Milne N, Brunnemann SR, Lyons KP. Metoclopramide-induced normalization of impaired gastric emptying in spinal cord injury. Am J Gastroenterol 1987;82(11):1143-8.
9. Milne N, Segal JL, Rypins EB, et al. Biliary kinetics in spinal cord injury. Presented at the 34th annual meeting of the society of nuclear medicine. Toronto, Ontario, Canada, June 2-5, 1987.
10. Pollock LJ, Boshes B, Chor H, et al. Defects in regulatory mechanisms of autonomic function in injuries to spinal cord. J Neurophys 1951;14:85-93.
11. Bannister R. Autonomic failure: a textbook of clinical disorders of the autonomic nervous system, 2nd ed. New York: Oxford University Press, 1988.
12. Greenhoot JH, Mauck HP. The effect of cervical cord injury on cardiac rhythm and conduction. Am Heart J 1972;83:659-62.
13. Bach JR. Alternative methods of ventilatory support for the patient with ventilatory failure due to spinal cord injury. J Am Paraplegia Soc 1991;14:158-74.
14. Vaziri ND, Eltorai IM, Segal J, et al. Erythropoietin profile in spinal cord injured patients. Arch Phys Med Rehabil 1993;74:65-7.
15. Segal JL, Brunnemann SR. Altered catecholamine levels are associated with changes in hepatic oxidative metabolism in humans with spinal cord injury. Presented at the 46th annual meeting of the American Paraplegia Society, Las Vegas, NV, September 2000.
16. Prete PE, Henbest M, Michalski JP, Porter RW. Intraspinal elastofibroma. A case report. Spine 1983;8(7):800-2.
17. Pobedina VG, Gelfand VB. Functional activity of blood leukocytes in the presence of traumatic lesions of the spinal cord. Zh Vopr Neirokhir 1977;5:25-8.
18. Duckworth WC, Solomon SS, Jallepalli P, et al. Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Diabetes 1980;29:906-10.
19. Karlsson A, Attvall S, Jansson P-A, Sullivan L, Lonroth P. Influence of the sympathetic nervous system on insulin sensitivity and adipose tissue metabolism: a study in spinal cord-injured subjects. Metabolism 1995;44(1):52-8.
20. Gowen M, Wood DD, Ihrie EJ, et al. An IL 1 like factor stimulates bone resorption in vitro. Nature 1983;306:378-80.
21. Miese AM, Willey JS, Bateman TA. Potential role of proinflammatory cytokines in nerve damage related bone loss. Biomed Sci Instrum 2004;40:266-71.
22. Downey JA, Huckaba CE, Myers SJ, Darling RC. Thermoregulation in spinal man. J Appl Physiol 1969;27:209-12.
23. Nash MS. Immune responses to nervous system decentralization and exercise in quadriplegia. Med Sci Sports Exerc 1994;26(2):164-71.
24. Nash MS. Known and plausible modulators of depressed immune functions following spinal cord injuries. J Spinal Cord Med 2000;23(2):111-20.
25. Slade JM, Bickel CS, Modlesky CM. Trabecular bone is more deteriorated in spinal cord versus estrogen-free postmenopausal women [online article ahead of print]. Osteoporosis Int, Aug 28, 2004.
26. Oppenheim JJ. Interleukins and interferons in inflammation. In: Current concepts. Kalamazoo, MI: The Upjohn Company, 1986.
27. Isaksson J, Farooque M, Holtz A, et al. Expression of ICAM-1 and CD11b after experimental spinal cord injury in rats. J Neurotrauma 1999;16(2):165-73.
28. Segal JL, Gonzales E, Yousefi S, et al. Circulating levels of IL-2R, ICAM-1, and IL-6 in spinal cord injuries. Arch Phys Med Rehabil 1977;78(1):44-7.
29. Cruse JM, Lewis RE, Bishop GR, et al. Adhesion molecules and wound healing in spinal cord injury. Pathobiology 1996;64(4):193-7.
30. Farooque M, Isaksson J, Olsson Y. White matter preservation after spinal cord injury in ICAM-1/P-selectin deficient-mice. Acta Neuropathol (Berl) 2001;102(2):132-40.
31. Smith KA, Cantrell DA. IL 2 regulates its own receptors. Proc Natl Acad Sci USA 1985;82:864-8.
32. Weber JS, Yang JC, Topalian SL, et al. The use of interleukin-2 and lymphokine-activated killer cells for the treatment of patients with non-Hodgkin's lymphoma. J Clin Oncol 1992;10(1):33-40.
33. Mitchell MS. Biomodulators in cancer treatment. J Clin Pharmacol 1992;32:2-9.
34. Fridman WH, Michon J. Pathophysiology of cytokines. Leuk Res 1990;14(8):675-7.
35. Siegel JP, Puri RK. Interleukin-2 toxicity. J Clin Oncol 1991;9(4):694-704.
36. Gaynor ER, Vitek L, Sticklin L, et al. The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1998;109:953-8.
37. Welbourn R, Goldman G, Kobzik L, et al. Interleukin-2 induces early multisystem organ edema mediated by neutrophils. Ann Surg 1991;214(2):181-6.
38. Harms BA, Pahl AC, Pohlman TH, et al. Effects of interleukin-2 on pulmonary and systemic transvascular fluid filtration. Surgery 1989;106(2):339-45.
39. Streeten DHP, ed. Orthostatic disorders of the circulation: mechanisms, manifestations, and treatment. New York: Plenum Publishing, 1987.
40. Kampschmidt RF. The numerous postulated biological manifestations of interleukin-1. J Leukocyte Biol 1984;36: 341-55.
41. Smith KA. Interleukin 2. Ann Rev Immunol 1984;2:319-33.
42. Saperstein A, Brand H, Audhya T, et al. Interleukin la mediates stress-induced immunosuppression via corticotropin-releasing factor. Endocrinology 1992;130(1):152-8.
43. Hirano T. Interleukin-6 and its relation to inflammation and disease. Clin Immunol Immunopathol 1992;62(1 pt 2):S60-5.
44. Nathan C, Sporn M. Cytokines in context. J Cell Biol 1991;113:981-6.
45. Bocci V. Interleukins: clinical pharmacokinetics and practical implications. Clin Pharmacokinet 1991;21(4):274-84.
46. Dinarello CA. Interleukin-1 and its biologically related cytokines. Adv Immunol 1989;44:153-205.
47. Greenway RM, Houser HB, Lindan O, Weir DR. Long-term changes in gross body composition of paraplegic and quadriplegic patients. Paraplegia 1970;7:301-8.
48. Shizgal HM, Roza A, Leduc B, et al. Body composition in quadriplegic patients. J Parenter Enteral Nutr 1986;10(4):364-8.
49. Rasmann Nuhlicek DN, Spurr GB, Barboriak JJ, et al. Body composition of patients with spinal cord injury. Eur J Clin Nutr 1988;42:765-73.
50. Segal JL, Gray DR, Gordon SK, et al. Gentamicin disposition kinetics in humans with spinal cord injury. Paraplegia 1985;23:47-55.
51. Dager WE. Aminoglycoside pharmacokinetics: volume of distribution in specific adult patient subgroups. Ann Pharmacother 1994;28:944-51.
52. Segal JL, Brunnemann SR, Gordon SK, Eltorai IM. Amikacin pharmacokinetics in patients with spinal cord injury. Pharmacotherapy 1988;8(2):79-81.
53. Segal JL, Gilman TM, Brunnemann SR. A nonparametric alternative to modeling population pharmacokinetics in patients with spinal cord injury: comparison with the standard two-stage method. Am J Ther 1995;2:100-5.
54. Segal JL, Hayes KC, Brunnemann SR, et al. Absorption characteristics of sustained release 4-aminopyridine (Fampridine SR) in patients with chronic spinal cord injury. J Clin Pharmacol 2000;40:402-9.
55. Bidart Y, Durand J, Martineaud JP. The nervous control of peripheral venous constriction at the beginning of exercise: comparative study in normal man and in paraplegia due to section of the dorsal spinal cord [in French]. Pathol Biol (Paris) 1971;19(12):13-19.
56. Plantin LO, Ahlinder S, Norberg R, Birke G. The distribution of proteins between intra- and extravascular spaces in health and disease. Acta Med Scand 1971;189:309-14.
57. Atkinson JP, Waldmann TA, Stein SF, et al. Systemic capillary leak syndrome and monoclonal IgG gammopathy: studies in a sixth patient and a review of the literature. Medicine 1977; 56(3):225-39.
58. Streeten DHP. Idiopathic edema: pathogenesis, clinical features and treatment. Metabolism 1987;27:353-83.
59. Cicardi M, Gardinali M, Bisiani G, et al. The systemic capillary leak syndrome: appearance of interleukin-2-receptor-positive cells during attacks. Ann Intern Med 1990;113:475-7.
60. Horwith M, Hagstrom JWC, Riggins RCK, Luckey E. Hypovolemic shock and edema due to increased capillary permeability. JAMA 1967;200:101-4.
61. Behar A, Tournoux A, Baillet J, Lagrue G. Untersuchungen zer bestimmung der kapillaren durchlässigkeit mit markiertem menschlichem albumin. Nuc Med 1976;15:214-16.
62. Albin MS, Buneguin L, Wolf S. Brain and lungs at risk after cervical spinal cord transection: intracranial pressure, brain water, blood-brain barrier permeability, cerebral blood flow, and extravascular lung water changes. Surg Neurol 1985;24(2):191-205.
63. Segal JL, Brunnemann SR. Circulating levels of soluble interleukin 2 receptors are elevated in the sera of humans with spinal cord injury. J Am Paraplegia Soc 1992;16(1):30-3.
64. Saito M, Akiyoshi M, Shimizu Y. Possible role of the sympathetic nervous system in responses to interleukin-1. Brain Res Bull 1991;27(3-4):305-8.
65. Ellison MD, Krieg RJ, Merchant RE. Cerebral vasomotor responses after recombinant interleukin 2 infusion. Cancer Res 1990;50(14):4377-81.
66. Amador JF, Vazquez AM, Cabrera L, et al. Toxic effects of interleukin-2-activated lymphocytes on vascular endothelial cells. Nat Immun Cell Growth Regul 1991;10:207-15.
67. Haugen PK, Letourneau PC. Interleukin-2 enhances chick and rat sympathetic, but not sensory, neurite outgrowth. J Neurosci Res 1990;25(4):443-52.
68. Plata-Salaman CR. Immunomodulators and feeding regulation: a humoral link between the immune and nervous systems. Brain Behav Immun 1989;3(3):193-213.
69. Maisel AS, Harris T, Rearden CA, Michel MC. Beta-adrenergic receptors in lymphocyte subsets after exercise: alterations in normal individuals and patients with congestive heart failure. Circulation 1990;82:2003-10.
70. Su TP, London ED, Jaffe JH. Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems. Science 1988;240:219-21.
71. Banks WA, Kastin AJ. Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci 1991;48(25):PL117-21.
72. Berkenbosch F, de Goeij DE, Rey AD, Besedovsky HD. Neuroendocrine, sympathetic and metabolic responses induced by interleukin-1. Neuroendocrinology 1989;50(5): 570-6.
73. Palazzolo DL, Quadri SK. Interleukin-1 stimulates catecholamine release from the hypothalamus. Life Sci 1990;47(23):2105-9.
74. Cruse JM, Lewis RE, Roe DL, et al. Facilitation of immune function, healing of pressure ulcers, and nutritional status in spinal cord injury patients. Exp Mol Pathol 2000;68(1):38-54.
75. Campagnolo DI, Bartlett JA, Keller SE. Influence of neurological level on immune function following spinal cord injury. J Spinal Cord Med 2000;23(2):121-8.
76. Dimova-Apostolova G, Angelova A, Vaaptzarova K. Catecholamine concentration in rat liver after high level transection of the spinal cord. Life Sci 1999;64(25):2375-81.
77. Black IB, Axelrod J. Inhibition of tyrosine transaminase activity by norepinephrine. J Biol Chem 1969;244(22):6124-9.
78. Ansher S, Thompson W, Habig W. Vaccine-induced alterations in hepatic drug metabolism. Vaccine 1991;9:227-83.
79. Eizirik DL, Bendtzen K, Sandler S. Short exposure of rat pancreatic islets to interleukin-1 beta induces a sustained but reversible impairment in beta-cell function: influence of protease activation, gene transcription, and protein synthesis. Endocrinology 1991;128(3):1611-16.
80. Ghezzi P, Saccardo B, Bianchi M. Recombinant tumor necrosis factor depressed cytochrome P-450-dependent microsomal drug metabolism in mice. Biochem Biophys Commun 1986;136:316-21.
81. Cantoni L, Rossi C, Rizzardini M, et al. Interleukin-1 and tumor necrosis factor induce hepatic haemoxygenase: feedback regulation by glucocorticoids. Biochem J 1991;279(3):891-4.
82. Hanto DW, Harty JT, Hoffman RA, Simmons RL. Evidence that secondary mixed leukocyte culture supernatant mediates changes in cellular recruitment, blood flow, and vascular permeability. Transplantation 1986;42(6):621-7.
83. Jesmok GJ, Gunther RA. In vivo biology of recombinant interleukin-2 infusion in sheep: cardiopulmonary manifestations of an intravascular immune-inflammatory response. Inflammation 1989;13(3):267-84.
84. Ellison MD, Krieg RJ, Merchant RE. Cerebral vasomotor responses after recombinant interleukin 2 infusion. Cancer Res 1990;50(14):4377-81.
85. Segal JL, Brunnemann SR, Eltorai IM, Vulpe M. Decreased systemic clearance of lorazepam in humans with spinal cord injury. J Clin Pharmacol 1991;31(7):651-6.
86. Segal JL, Brunnemann SR, Casteñeda-Hernádez G, Guizar-Sahagun G. Altered hepatocyte gene expression in a rat model of chronic spinal cord injury [abstr]. J Clin Pharmacol 2000;40:1045.
87. Lipetz JS, Kirshblum SC, O'Conner KC, Voorman SJ, Johnston MV. Anemia and serum protein deficiencies in patients with traumatic spinal cord injury. J Spinal Cord Med 1997;20(3):335-40.
88. Segal JL, Eltorai IM, Brunnemann SR, Gilman T. Pharmacokinetics of amikacin in serum and in tissue contiguous with pressure sores in humans with spinal cord injury. Antimicrobial Agents Chemother 1990;34(7):1422-8.
89. Darouiche RO, Landon GC, Klima M, et al. Osteomyelitis associated with pressure sores. Arch Intern Med 1994;154(7):753-8.
90. Cruse JM, Keith JC, Bryant ML Jr, Lewis RE Jr. Immune system-neuroendocrine dysregulation in spinal cord injury. Immunol Res 1996;15(4):306-14.
91. Campagnolo DI, Bartlett JA, Keller SE, et al. Impaired phagocytosis of Staphylococcus aureus in complete tetraplegics. Am J Phys Med Rehabil 1997;76(4):276-80.
92. Rodriguez DJ, Clevenger FW, Osler TM, et al. Obligatory negative nitrogen balance following spinal cord injury. J Parenter Enteral Nutr 1991;15(3):319-22.
93. Rodriguez GP, Claus-Walker J. Biochemical changes in skin composition in spinal cord injury: a possible contribution to decubitus ulcers. Paraplegia 1988;26:302-9.
94. Rodriguez GP, Garber SL. Prospective study of pressure ulcer risk in spinal cord injury patients. Paraplegia 1994;32(3):150-8.
95. Dummer R, Miller K, Eilles CH, Burg G. The skin: an immunoreactive target organ during interleukin-2 administration? Dermatologica 1991;183:95-9.
96. Baracor V, Rodemann HP, Dinarello CA, Goldberg AL. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1): a mechanism for the increased degradation of muscle proteins during fever. N Engl J Med 1983;308:553-8.
97. Zamir O, Hasselgran PO, von Allemen D, Fischer JE. The effect of interleukin-IA and the glucocorticoid receptor blocker RU 38486 on total and myofibrillar protein breakdown in skeletal muscle. J Surg Res 1991;50:579-83.
98. Everts V, Wolvius E, Saklatvala J, Beertsen W. Interleukin 1 increases the production of collagenase but does not influence the phagocytosis of collagen fibrils. Matrix 1990;10:388-93.
99. Raynes JG, Eagling S, McAdam KP. Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6. Clin Exp Immunol 1991;83(3):488-91.
100. Yap SH, Moshage HJ, Hazenberg BP, et al. Tumor necrosis factor (TNF) inhibits interleukin (IL)-1 and/or IL-6 stimulated synthesis of C-reactive protein (CRP) and serum amyloid A (SAA) in primary cultures of human hepatocytes. Biochim Biophys Acta 1991;1091(3):405-8.
101. Blume AJ, Vitek MP. Focusing on IL-1-promotion of beta amyloid precursor protein synthesis as an early event in Alzheimer's disease. Neurobiol Aging 1989;10(5):406-8.
102. Araujo DM, Cotman CW. Beta-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer's disease. Brain Res 1992;569(1):141-5.
103. Ohry A, Shemesh Y, Rozin R. Are chronic spinal cord injured persons prone to premature aging? Med Hypotheses 1983;11:467-9.
104. Blumenthal HT, Premachandra BN. Bridging the aging-disease dichotomy. I. The amyloidosis model. Perspect Biol Med 1990;33(3):402-20.
105. Rifas L, Shen V, Mitchel K, Peck W. Macrophage derived growth factor for osteoblast-like cells and chondrocytes. Proc Natl Acad Sci USA 1984;81:4558-62.
106. Kurer MHJ, Khoker MA, Dandona P. Human osteoblast stimulation by sera from paraplegic patients with heterotopic ossification. Paraplegia 1992;30:165-8.
107. Demulder A, Guns M, Ismail A, et al. Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with spinal cord injury. Calcif Tissue Int 1998;63(5):396-400.
108. Banovac K. The effect of etidronate on late development of heterotopic ossification after spinal cord injury. J Spinal Cord Med 2000;23(1):40-4.
109. Nash MS, Tehranzadeh J, Green BA, et al. Magnetic resonance imaging of osteonecrosis and osteoarthrosis in exercising quadriplegics and paraplegics. Am J Phys Med Rehabil 1994;73(3):184-92.
110. Colten HR. Tissue-specific regulation of inflammation. J Appl Physiol 1992;72(1):1-7.
111. Mechanick JI, Pomerantz F, Flanagan S, Stein A, Gordon WA, Ragnarsson KT. Parathyroid hormone suppression in spinal cord injury patients is associated with the degree of neurologic impairment and not the level of injury. Arch Phys Med Rehabil 1997;78(7):692-6.
112. Richardson HJ, Elford PR, Sharrard RM, et al. Modulation of connective tissue metabolism by partially purified human IL 1. Cell Immunol 1985;90:41-51.
113. Lowik CW, van der Pluijm G, Bloys H, et al. Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclastogenesis. Biochem Biophys Res Comm 1989;162(3):1546-52.
114. Feyen JH, Elford P, Di Padova FE, Trechsel U. Interleukin-6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res 1989;4(4):633-8.
115. Li N, Ouchi Y, Okamoto Y, et al. Effect of parathyroid hormone on release of interleukin 1 and interleukin 6 from cultured mouse osteoblastic cells. Biochem Biophys Res Commun 1991;179(1):236-42.
116. Pietschmann P, Pils P, Woloszczuk W, et al. Increased serum osteocalcin levels in patients with paraplegia. Paraplegia 1992;30:204-9.
117. La Porte RE, Brenes G, Dearwater S, et al. HDL cholesterol across a spectrum of physical activity from quadriplegia to marathon running. Lancet 1983;1(8335):1212-13.
118. Heldenberg D, Rubinstein A, Levtov O, et al. Serum lipids and lipoprotein concentrations in young quadriplegic patients. Atherosclerosis 1981;39:163-7.
119. Zawalich WS, Diaz VA. Interleukin 1 inhibits insulin secretion from isolated perfused rat islets. Diabetes 1986;35(10):1119-23.
120. Gagner M, Shizgal HM, Forse RA. The effect of interleukin-1 and interleukin-2 on the adrenergic control of hormone-sensitive lipase in the human adipocyte. Surgery 1986;100(2):298-305.
121. Eizirik DL, Tracey DE, Bendtzen K, Sandler S. An interleukin-1 receptor antagonist protein protects insulin-producing beta cells against suppressive effects of interleukin-1 beta. Diabetologia 1991;34:445-8.
122. Berczeller PH, Bexkor MF, eds. Medical complications of quadriplegia. Chicago: Year Book Medical Publishers, Inc., 1986.
123. Mathias CJ. Role of sympathetic efferent nerves in blood pressure regulation and in hypertension. Hypertension 1991;18(suppl 5):III22-30.
124. Nora R, Abrams JS, Tait NS, et al. Myocardial toxic effects during recombinant interleukin-2 therapy. J Natl Cancer Inst 1989;81:59-63.
125. Isoda WC, Segal JL. Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury. Pharmacotherapy 2003;23(2):133-6.
126. Goel M, Flaherty L, Lavine S, Redman BG. Reversible cardiomyopathy after high-dose interleukin-2 therapy. J Immunother 1992;11(3):225-9.
127. Collins S, Caron MG, Lefkowitz RJ. Regulation of adrenergic receptor responsiveness through modulation of receptor gene expression. Ann Rev Physiol 1991;53:497-508.
128. Rivier C, Vale W, Brown M. In the rat, interleukin-1 alpha and beta stimulate adrenocorticotropin and catecholamine release. Endocrinology 1989;125(6):3096-102.
129. Plata-Salamán CR. Immunoregulators in the nervous system. Neurosci Biobehav Rev 1991;15:185-215.
130. Klausner JM, Paterson IS, Goldman G, et al. Interleukin-2-induced lung injury is mediated by oxygen free radicals. Surgery 1991;109:169-75.
131. Frisbie JH, Kache A. Increasing survival and changes in causes of death in myelopathy patients. J Am Paraplegia Soc 1983;6(3):51-9.
132. Poe RH, Reisman JL, Rodenhouse TG. Pulmonary edema in cervical spinal cord injury. J Trauma 1978;18:71-3.
133. Hudson LD. Causes of the adult respiratory distress syndrome clinical recognition. Clin Chest Med 1982;3:195-212.
134. Halstead LS, Feldman S, Claus-Walker J, Patel VC. Drug absorption in spinal cord injury. Arch Phys Med Rehabil 1985;66:298-301.
135. Glick ME, Meshkinpour H, Haldeman S, et al. Colonic dysfunction in patients with thoracic spinal cord injury. Gastroenterology 1984;86:287-94.
136. 2 synthesis by the stomach, and retards gastric emptying. Life Sci 1991;48(2):123-34.
137. Uehara A, Okumura T, Kitamori S, et al. Interleukin-1: a cytokine that has potent antisecretory and anti-ulcer actions via the central nervous system. Biochem Biophys Res Commun 1990;173(2):585-90.
138. Leramo OB, Tator CH, Hudson AR. Massive gastroduodenal hemorrhage and perforation in acute spinal cord injury. Surg Neurol 1982;17(3):186-90.
139. Tanaka M, Uchiyama M, Kitano M. Gastroduodenal disease in chronic spinal cord injuries. Arch Surg 1979;114:185-7.
140. Kewalramani IS. Neurogenic gastroduodenal ulceration and bleeding associated with spinal cord injuries. J Trauma 1979;19:259-65.
141. Hirsch GH, Menard MR, Anton HA. Anemia after traumatic spinal cord injury. Arch Phys Med Rehabil 1991;72(3):195-201.
142. DeRienzo DP, Saleem A. Anemia of chronic disease: a review of pathogenesis. Tex Med 1990;86(10):80-3.
143. Claus-Walker J, Dunn CDR. Spinal cord injury and serum erythropoietin. Arch Phys Med Rehabil 1984;65:370-4.
144. Ascensao JL, Liu SJ, Caro J, et al. Erythropoiesis in cancer patients undergoing immunotherapy. Adv Exp Med Biol 1989;271:197-204.
145. Rossini F, Brivio F, Mingozzi S, et al. Thrombocytosis, neutrophilia and anemia during interleukin-2 therapy. Haematologica 1991;76(5):439-40.
146. Hachen HJ, Rossier AB, Bouvier CA, Ritschard J. Deficiency within the extrinsic prothrombin activator system in patients with acute spinal cord injury. Paraplegia 1974;12:132-8.
147. Bevilacqua MP, Pober JS, Majeau GR, et al. Interleukin 1 (IL 1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984;160:618-23.
148. Vaziri ND, Patel B, Alikhami A, et al. Protein C abnormalities in spinal cord injured patients with end-stage renal disease. Arch Phys Med Rehabil 1987;68(11):791-3.
149. Leist M, Ghezzi P, Grasso G, et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004;305(5681):239-42.
150. Nakashima T, Hori T, Mori T, et al. Recombinant human interleukin-1 beta alters the activity of preoptic thermosensitive neurons in vitro. Brain Res Bull 1989;23(3):209-13.
151. Dinarello CA. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med 1984;311(22):1413-18.
152. Turchik JB, Bornstein DL. Role of the central nervous system in acute-phase responses to leukocytic pyrogen. Infect Immun 1980;32(2):439-44.
153. Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 1988;8(7):2485-90.
154. Jones TB, Basso DM, Sodhi A. Pathological CNS autoimunne disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 2002;22(7): 2690-700.
155. Tzeng SF, Kahn M, Liva S, De Vellis J. Tumor necrosis factor-alpha regulation of the Id gene family in astrocytes and microglia during CNS inflammatory injury. Glia 1999;26(2):139-52.
156. Pan W, Kastin AJ, Bell RL, Olson RD. Upregulation of tumor necrosis factor alpha transport across the blood-brain barrier after acute compressive spinal cord injury. J Neurosci 1999;19(9):3649-55.
157. Blesch A, Uy HS, Grill RJ, et al. Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. J Neurosci 1999;19(9): 3556-66.
158. McClan C, Cohen D, Phillips R, et al. Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury. J Lab Clin Med 1991;188(3):225-31.
159. Giulian D, Baker TJ, Lachman LB. Brain injury induces release of interleukin-1 from activated microglia [abstr]. J Leukocyte Biol 1985;37:707.
160. Robertson CS. Inflammatory cells and the hypermetabolism of head injury [letter]. J Lab Clin Med 1991;118(3):205.
161. Giulian D, Chen J, Ingeman JE, George JK, Noponen M. The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci 1989;9(12):4416-29.
162. Farooque M, Isaksson J, Olsson Y. Improved recovery after spinal cord trauma in ICAM-1 and P-selectin knockout mice. Neuroreport 1999;10(1):131-4.
163. Dinarello CA, Thompson RC. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 1991;12(11):404-10.
164. Giulian D, Robertson C. Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 1990;27:33-42.
165. Klusman I, Schwab ME. Effects of pro-inflammatory cytokines in experimental spinal cord injury. Brain Res 1997;762(1-2):173-84.