Plasma endothelin-1, cytokine, and prostaglandin E2 levels in sickle cell disease and acute vaso-occlusive sickle crisis.

The relative contributions of microvascular inflammation and vasomotor dysregulation to the development of acute vaso-occlusive crisis in sickle cell disease have been intensely studied. The present observational study was designed to examine the levels of circulating proinflammatory cytokines, anti-inflammatory cytokines, and vasoactive mediators during and after acute painful crisis. In symptomatic sickle cell patients, plasma levels of endothelin-1 and prostaglandin E2 were elevated during crises compared with healthy African-American controls. These levels had decreased, but not normalized, when patients were seen 1 to 3 weeks after discharge from hospital. Other mediators (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], IL-6, IL-8, and IL-10) were neither elevated in asymptomatic sickle cell disease nor in acute vaso-occlusive crisis. As a potent long-acting mediator of vasoconstriction and inflammation, endothelin-1 may play a key role in the cycle of ischemia and inflammation that initiates and sustains pain of crisis. The downregulatory effects of prostaglandin E2 on immune cell function may contribute to the increased susceptibility to infection observed in patients with sickle cell disease.

[1]  L. Haywood,et al.  Elevated immunoreactive tumor necrosis factor and interleukin-1 in sickle cell disease. , 1992, Journal of the National Medical Association.

[2]  R. J. Bala,et al.  Endothelin-1 and endothelin-4 stimulate monocyte production of cytokines. , 1997, Critical care medicine.

[3]  J. Vane,et al.  The biosynthesis of endothelin-1 by human polymorphonuclear leukocytes. , 1991, Biochemical and biophysical research communications.

[4]  J. Huidobro-Toro,et al.  Endothelin reduces microvascular blood flow by acting on and venules of the hamster cheek pouch , 1990 .

[5]  K. Lenz,et al.  Endothelin-1 in adult respiratory distress syndrome. , 1993, The American review of respiratory disease.

[6]  P. Vanhoutte,et al.  Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. , 1985, The Journal of physiology.

[7]  D. Pollock,et al.  Endothelin receptors and calcium signaling 1 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  D. Gemsa,et al.  Release of cyclic AMP from macrophages by stimulation with prostaglandins. , 1975, Journal of immunology.

[9]  M. Mosseri,et al.  Inhibition of endothelium-dependent vasorelaxation by sickle erythrocytes. , 1993, American heart journal.

[10]  D. Gómez-Garre,et al.  Aggregation of human polymorphonuclear leukocytes by endothelin: role of platelet-activating factor. , 1992, European journal of pharmacology.

[11]  P. Gasparini,et al.  Increased Levels of Endothelin-1 in Plasma of Sickle Cell Anemia Patients , 1998 .

[12]  E. Unanue,et al.  The functional significance of the regulation of macrophage Ia expression by endogenous arachidonate metabolites in vitro. , 1986, Journal of immunology.

[13]  A. Sasco,et al.  Cell-mediated immunity in patients with sickle cell anaemia. , 1988, Thymus.

[14]  B. Sumpio,et al.  Endothelial cell control of vasomotor tone , 1995, Annals of vascular surgery.

[15]  J. Huidobro-Toro,et al.  Endothelin reduces microvascular blood flow by acting on arterioles and venules of the hamster cheek pouch. , 1990, European journal of pharmacology.

[16]  E. Wayner,et al.  Integrin alpha 4 beta 1 and glycoprotein IV (CD36) are expressed on circulating reticulocytes in sickle cell anemia , 1993 .

[17]  G. R. Dodge,et al.  Prostaglandin E inhibits the production of human interleukin 2 , 1982, The Journal of experimental medicine.

[18]  R. Kumar,et al.  Endothelin-stimulated human monocytes produce prostaglandin E2 but not leukotriene B4. , 1993, The Journal of surgical research.

[19]  Y. Kilinç,et al.  Immunological studies in sickle cell disease: comparison of homozygote mild and severe variants. , 1989, Clinical immunology and immunopathology.

[20]  R. Sorensen,et al.  New concepts in the immunology of sickle cell disease. , 1996, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[21]  D. Golan,et al.  Adhesion of sickle neutrophils and erythrocytes to fibronectin. , 1996, Blood.

[22]  T. Pearson,et al.  Red blood cells from patients with sickle cell disease exhibit an increased adherence to cultured endothelium pretreated with tumour necrosis factor (TNF) , 1992, British journal of haematology.

[23]  R. Marttila,et al.  Decreased raphe serotonin in rabbits with experimental herpes simplex encephalitis , 1993, Neuroscience Letters.

[24]  H. Farber,et al.  Endothelin-1 production during the acute chest syndrome in sickle cell disease. , 1997, American journal of respiratory and critical care medicine.

[25]  H. Krum,et al.  The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. , 1998, The New England journal of medicine.

[26]  M. Steinberg,et al.  Sickle cell anemia: Erythrokinetics, blood volumes, and a study of possible determinants of severity , 1977, American journal of hematology.

[27]  B. G. Sparkes.  Immune consequences of trauma, shock and sepsis , 1990 .

[28]  R. Westendorp,et al.  Anti-inflammatory cytokine profile and mortality in febrile patients , 1998, The Lancet.

[29]  P. Marrack,et al.  Effect of prostaglandin E2 on the γ-interferon induction of antigen-presenting ability in P388D1 cells and on IL-2 production by T-cell hybridomas , 1985 .

[30]  R. McCarron,et al.  Endothelin induction of adhesion molecule expression on human brain microvascular endothelial cells , 1993, Neuroscience Letters.

[31]  H. Furue,et al.  Plasma endothelin-1 levels in patients with disseminated intravascular coagulation. , 1991, The New England journal of medicine.

[32]  R. Kumar,et al.  Endothelin-1 increases intracellular calcium in human monocytes and causes production of interleukin-6. , 1995, Critical care medicine.

[33]  J. Ninnemann,et al.  Participation of prostaglandin E in immunosuppression following thermal injury. , 1984, The Journal of trauma.

[34]  R. Kumar,et al.  ENDOTHELIN‐STIMULATED MONOCYTE SUPERNATANTS ENHANCE NEUTROPHIL SUPEROXIDE PRODUCTION , 1994, Shock.

[35]  B. Sumpio,et al.  Endothelins: polyfunctional cytokines. , 1995, Journal of the American College of Surgeons.

[36]  G. Rao,et al.  Chemotaxis of human blood monocytes toward endothelin-1 and the influence of calcium channel blockers. , 1992, Biochemical and biophysical research communications.

[37]  Sadao Kimura,et al.  A novel potent vasoconstrictor peptide produced by vascular endothelial cells , 1988, Nature.

[38]  J. Vane,et al.  Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[39]  L. Thijs,et al.  Plasma endothelin levels are increased during septic shock , 1992, Critical care medicine.

[40]  D. Faller,et al.  Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture. , 1995, The Journal of clinical investigation.

[41]  S. Kunkel,et al.  Arachidonic acid metabolites regulate interleukin-1 production. , 1985, Biochemical and biophysical research communications.

[42]  L. Parise,et al.  Integrin alpha 4 beta 1 and glycoprotein IV (CD36) are expressed on circulating reticulocytes in sickle cell anemia. , 1993, Blood.

[43]  A. Doherty,et al.  Characterization of endothelins as chemoattractants for human neutrophils. , 1994, Life sciences.