Conceptos Categóricos

INMUNOTERAPIA, NUEVAS PERSPECTIVAS Y NUEVOS INTERROGANTES

INMUNOTERAPIA, NUEVAS PERSPECTIVAS Y NUEVOS INTERROGANTES

(especial para SIIC © Derechos reservados)
La IL-10 recombinante humana ha sido evaluada en muchos ensayos clínicos de fases I y II en patologías como artritis reumatoidea, enfermedad inflamatoria intestinal, psoriasis, trasplante de órganos y hepatitis C. Los resultados clínicos han sido heterogéneos y sugieren que la IL-10 se adecua mejor a prolongar la remisión y prevenir la recurrencia de enfermedades inflamatorias que a tratar las exacerbaciones agudas.
asadullah9.jpg Autor:
Khusru Asadullah
Columnista Experto de SIIC

Institución:
Corporate Research Business Area Inflammation, Schering AG


Artículos publicados por Khusru Asadullah
Coautores
Robert Sabat*  Markus Friedrich*  Wolf-Dietrich Döcke**  Hans Dietrich Volk***  Wolfram Sterry**** 
Interdisciplinary Group of Molecular Immnunopathology, Dermatology / Medical Immunology*
Corporate Research Business Area Inflamation, Schering AG,**
Insititute of Medical Immunology, University Hospital Charité***
Departments of Dermatology and Allergology, University Hospital Charité****
Recepción del artículo
29 de Diciembre, 2005
Aprobación
30 de Diciembre, 2005
Primera edición
1 de Junio, 2006
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La interleuquina (IL) 10 es una citoquina importante que es producida por muchas poblaciones celulares. Numerosas investigaciones, incluidas los análisis de expresión, sugirieron la importancia fisiopatológica de la IL-10. Esta molécula está sobreexpresada en muchos tumores y se considera que promueve el crecimiento tumoral. Por el contrario, en algunos trastornos inflamatorios caracterizados por un patrón de citoquinas de tipo 1 como la psoriasis, se observó un déficit relativo de IL-10, el cual adquirió importancia fisiopatológica. En este sentido, la capacidad de la IL-10 de limitar y terminar las respuestas inflamatorias y regular la diferenciación y proliferación de una variedad de células inmunes la han vuelto una droga de interés. La IL-10 recombinante humana ha sido evaluada en muchos ensayos clínicos de fases I y II en artritis reumatoidea, enfermedad inflamatoria intestinal, psoriasis, trasplante de órganos y hepatitis C. Los resultados clínicos son heterogéneos y muestran que la IL-10 se adecua mejor a prolongar la remisión y prevenir la recurrencia de enfermedades inflamatorias que a tratar las exacerbaciones agudas. Se necesitan más estudios que determinen mejor el perfil de acciones y efectos colaterales de esta molécula, así como las indicaciones terapéuticas adecuadas.

Palabras clave
citoquina, interleuquina, inmunoterapia, inflamación, psoriasis


Artículo completo

(castellano)
Extensión:  +/-13.86 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Interleukin (IL)-10 is an important cytokine produced by many cell populations. Numerous investigations, including expression analyses in patients suggested a major physiological and pathophysiological impact of IL-10. It is overexpressed in many tumors and considered to promote tumor development. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. In particular IL-10s ability to limit and terminate inflammatory responses and to regulate the differentiation and proliferation of several immune cells made it to an interesting drug candidate. Recombinant human IL-10 has been tested in several clinical phase 1 and 2 trials, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and hepatitis C. The clinical results are heterogeneous, and indicate that IL-10 is rather suited to prolong the remission / to prevent the reoccurrence of inflammatory diseases than to treat exacerbated acute disease stages. Further investigations are needed to better determine the effect / side effect profile as well as it suitable target indications.

Key words
cytokine, interleukin, immunotherapy, inflammation, psoriasis


Full text
(english)
para suscriptores/ assinantes

Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Inmunología
Relacionadas: Bioquímica, Dermatología, Farmacología, Gastroenterología, Medicina Farmacéutica, Medicina Interna, Trasplantes



Comprar este artículo
Extensión: 13.86 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Khusru Asadullah, Corporate Research Business Area Inflammation, Schering AG, 13342, Muellerstrasse 178, Berlín, Alemania
Patrocinio y reconocimiento:
Los autores agradecen a Stefanie Schoepe por la revisión del manuscrito. Los autores analizaron este tema previamente en otras publicaciones.
Bibliografía del artículo
1. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T-helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989; 170:2081-2095.
2. Spits H and De Waal Malefyt R 1992 Functional characterization of human IL-10. Int Arch Allergy Immunol 99:8-15.
3. Eskdale J, Gallagher G. A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogenetics. 1995; 42:444-445.
4. Eskdale J, Kube D, Gallagher G. A second polymorphic dinucleotide repeat in the 5' flanking region of the human IL10 gene. Immunogenetics. 1996; 45:82-83.
5. Platzer C, Meisel C, Vogt K, Platzer M, Volk HD. Up-regulation of monocytic IL 10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol. 1995; 7:517-523.
6. Platzer C, Fritsch E, Elstner T, Lehmann MH, Volk HD, Prosch S. Cyclic adenosine monophosphate-responsive elements are involved in the transcriptional activation of the human IL-10 gene in monocytic cells. Eur J Immunol. 1999; 29: 3098-3104.
7. Platzer C, Docke WD, Volk HD, Prosch S. Catecholamines trigger IL-10 release in acute systemic stress reaction by direct stimulation of its promoter/enhancer activity in monocytic cells. J Neuroimmunol. 2000; 105: 31-38.
8. Meisel C, Vogt K, Platzer C, Randow F, Liebenthal C, Volk HD. Differential regulation of monocytic tumor necrosis factor-alpha and interleukin-10 expression. Eur J Immunol. 1996; 26:1580-1586.
9. Woiciechowsky C, Asadullah K, Nestler D, et al. Sympathetic activation triggers systemic interleukin-10 release in immunoderession induced by brain injury. Nat Med. 1998; 4:808-813.
10. Riese U, Brenner S, Docke WD, et al. Catecholamines induce IL-10 release in patients suffering from acute myocardial infarction by transactivating its promoter in monocytic but not in T cells. Mol Cell Biochem. 2000; 212: 45-50.
11. Barsig J, Kusters S, Vogt K, Volk HD, Tiegs G, Wendel A. Lipopolysaccaride-induced IL-10 in mice: role of endogenous TNF-alpha. Eur J Immunol. 1995; 25: 2888-2893.
12. Jilg S, Barsig J, Leist M, Kusters S, Volk HD, Wendle A. Enhanced release of IL-10 and soluble TNF receptors as novelprinciples of methyxanthine action in murine models of endotoxic shock. J Pharmacol Exp Ther. 1996; 278: 421-431.
13. Ma W, Lim W, Gee K, et al. The p38 mitogen-activated kinase pathway regulates the human interleukin-10 promoter via the activation of Sp1 transcription factor in lipopolysaccharide-stimulated human macrophages. J Biol Chem. 2001; 276:13664-13674.
14. Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW. A receptor for interleukin 10 is related to interferon receptors. Proc Natl Acad Sci USA. 1993; 90:11267-11271.
15. Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S. Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J. 1997; 16:5894-5903.
16. Tan JC, Indelicato SR, Narula SK, Zavodny PJ, Chou CC. Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem. 1993; 268: 21053-21059.
17. Reineke U, Sabat R, Volk HD, Schneider-Mergener J. Mapping of the interleukin-10/interleukin-10 receptor combining site. Protein Sci. 1998; 7: 951-960.
18. Reineke U, Schneider-Mergener J, Glaser RW, et al. Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit1. 1999; 2:242-248.
19. Spencer SD, Di Marco F, Hooley J, et al. The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med. 1998; 187: 571-578.
20. Tanaka Y, Nakashima H, Nemoto Y, et al. Detection of polymorphisms within the human IL-10 receptor cDNA gene sequence by RT-PCR RFLP. Immunogenetics. 1997; 46: 439-441.
21. Carson WE, Lindemann MJ, Baiocchi R et al. The functional characterization of interleukin-10 receptor expression on human natural killer cells. Blood. 1995; 85:3577-3585.
22. Jurlander J, Lai CF, Tan J, et al. Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells. Blood. 1997; 89:4146-4152.
23. Weber-Nordt RM, Meraz MA, Schreiber RD. Lipopolysaccharide-dependent induction of IL-10 receptor expression on murine fibroblasts. J Immunol. 1994; 153: 3734-3744.
24. Michel G, Gailis A, Jarzebska-Deussen B, Muschen A, Mirmohammadsadegh A, Ruzicka T. 1,25-OH2-vitamin D3 and calcipotriol induce IL-10 receptor gene expression in human epidermal cells. Inflamm Res. 1997; 46:32-34.
25. Michel G, Mirmohammadsadegh A, Olasz E, et al. Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up-regulation by an antipsoriatic glucocorticosteroid in normal cultured keratinocytes. J Immunol. 1997; 159:6291-6297.
26. Liu Y, Wei SH, Ho AS, De Waal Malefyt R, Moore KW. Expression cloning and characterization of a human IL-10 receptor. J Immunol. 1994; 152:1821-1829.
27. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683-765.
28. Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995; 155:1079-1090.
29. Jung M, Sabat R, Krätzschmar J, et al. Expression profiling of IL-10 regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL-10 therapy, Eur J Immunol. 2004; 34:481-93.
30. Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin IL-10 inhibits nuclear factor kappa B NF kappa B activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem. 1995; 270:9558-9563.
31. Clarke CJP, Hales A, Hunt A, Foxwell BMJ. IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity. Eur J Immunol. 1998; 28:1719-1726.
32. Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJG. Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin Exp Immunol. 2004; 135:64-73.
33. Ito S, Ansari P, Sakatsume M, et al. Interleukin-10 inhibits expression of both interferon - and interferon -induced genes by suppressing tyrosine phosphorylation of STAT1. Blood. 1999; 93:1456-1463.
34. Yamaoka K, Otsuka T, Niiro H, et al. Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes. J. Interferon Cytokine Res. 1999; 19:679-85
35. Donelly RP, Dickensheets H, Finbloom DS. The Il-10 signal transduction pathway and regulation of gene expression in monunuclear phagocytes. J Interferon Cytokine Res. 1999; 19:563-573.
36. Berlato C, Cassatella MA, Kinjyo I, Gatto L, Yoshimura, Bazzoni F. Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory effects of IL-10 on LPS-induced macrophage activation. J Immunol. 2002; 168: 6404-6411.
37. Lee TS, Chau LY 2002 Heme oxygenase-1 mediates the anti-inflammatory effect of IL-10 in mice. Nat Med 8: 240-246.
38. Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy - review of a new approach. Pharmacology Rev. 2003; 55:241-69.
39. Blay JY, Burdin N, Rousset F et al. Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor. Blood. 1993; 82: 2169-2174.
40. Stasi R, Zinzani L, Galieni P, et al. Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma. Identification of a subset at high risk of treatment failure. Cancer. 1994; 74:1792-1800.
41. Stasi R, Zinzani L, Galieni P, et al. Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma. Br J Haematol. 1994; 88:770-777.
42. Cortes JE, Talpaz M, Cabanillas F, Seymour JF, Kurzrock R. Serum levels of interleukin-10 in patients with diffuse large cell lymphoma: lack of correlation with prognosis. Blood. 1995; 85: 2516-2520.
43. Ohmen JD, Hanifin JM, Nickoloff BJ, et al. Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. J Immunol. 1995; 154:1956-1963.
44. Chung F. Anti-inflammatory cytokines in asthma and allergy: IL-10, IL-12, interferon-gamma. Mediators Inflamm. 2001; 10: 51-59.
45. Takanashi S, Hasegawa Y, Kanehira Y, et al. IL-10 level in sputum is reduced in bronchial asthma, COPD and in smokers. Eur Respir J. 1999; 14: 309-314.
46. Lyons A, Kelly JL, Rodrick ML, Mannick JA, Lederer JA. Major injury induces increased production of IL-10 by cells of the immune system with a negative impact on resistance to infection. Ann Surg. 1997; 226: 450-458.
47. Van Dissel JT, van Langevelde P, Westendrop RG, Kwappenberg K, Frolich M. Anti-inflammatory cytokine profile and mortality in febril patients. Lancet. 1998; 351: 950-953.
48. Opal SM, Huber CE. The role of IL-10 in critical illness. Curr Opin Infect Dis. 2000; 13: 221-226.
49. Volk HD, Reinke P, Docke WD. Clinical aspects: from systemic inflammation to "immunoparalysis". Chem Immunol. 2000; 74: 162-177.
50. Muehlstedt SG, Lyte M, Rodriguez JL. Increased IL-10 production and HLA-DR suppression in the lungs of injured patients precede the development of nosocomial pneumonia. Shock. 2002; 17: 443-450.
51. Spies CD, Kern H, Schroder T, et al. Myocardial ischemia and cytokine response are asociated with subsequent onset of infections after noncardiac surgery. Anesth Analg. 2002; 95: 9-18.
52. Hsu DH, De Waal Malefyt R, Fiorentino DF, et al. Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science. 1990; 250:830-832.
53. Rode HJ, Bugert JJ, Handermann M, et al. Molecular characterization and determination of the coding capacity of the genome of equine herpesvirus type 2 between the genome coordinates 0.235 and 0.258 the EcoRI DNA fragment N; 4.2kbp. Virus Genes. 1994; 9:61-75.
54. Kotenko SV, Saccani S, Izotova LS, Mirochnitchenko OV, Pestka S. Human cytomegalovirus harbors its own unique IL-10 homolog cmv IL-10. Proc Natl Acad Sci USA. 2000; 97: 1695-1700.
55. Spencer JV, Lockridge KM, Barry PA, et al. Potent immunosuppressive activities of cytomegalovirus-encoded IL-10. J Virol. 2002; 76: 1285-1292.
56. Kline JN, Hunninghake GM, He B, Monick MM, Hunninghake GW. Synergistic activation of the human cytomegalovirus major immediate early promoter by prostaglandin E2 and cytokines Exp Lung Res. 1998; 24:3-14.
57. Redpath S, Ghazal P, Gascoigne NRJ. Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol. 2001; 9: 86-92.
58. Demangel C, Bertolino P, Britton WJ. Autocrine IL-10 impairs dendritic cell derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur J Immunol. 2002; 32: 994-1002.
59. Westendorp RG, Langermans JA, Huizinga TW, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997; 349:170-173.
60. Tambur AR, Ortegel JW, Ben-Ari Z, et al. Role of cytokine gene polymorphism in hepatitis C recurrence and allograft rejection among liver transplant recipients. Transplantation. 2001; 71: 1475-1480.
61. Zhang J, Chen H, Hu L, Fu J, Zhang H, Chen Y. Corrlation between polymorphism of IL-4 and IL-10 gene promoter and childhood asthma and their impact upon cytokine expression. Zhonghua Yi Xue Za Zhi. 2002; 82: 114-118.
62. McCarron SL, Edwards S, Evans PR, et al. Influence of cytokine gene polymorphisms on th edevelopment of prostate cancer. Cancer Res. 2002; 62: 3369-3372.
63. Wu MS, Huang SP, Chang YT, et al. TNF-alpha and IL-10 promoter polymorphisms in Epstein-Barr virus-associated gastric carcinoma. J Infect Dis. 2002; 185: 106-109.
64. Kaluza W, Leirisalo-Repo M, Marker-Hermann E, et al. IL-10G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finish patients. Arthritis Rheum. 2001; 44: 1209-1214.
65. Eskdale J, McNicholl J, Wordsworth P, et al. Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility (letter). Lancet. 1998; 352:1282-1283.
66. Turner DM, Grant SC, Yonan N, et al. Cytokine gene polymorphism and heart transplant rejection. Transplantation. 1997; 64: 776-779.
67. Takahashi H, Furukawa T, Hashimoto S, et al. Bone Marrow Transplant. 2000; 26: 1317-1323.
68. Asderakis A, Sankaran D, Dyer P et al. Association of polymorphisms in th ehuman interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: th ecytokine effect on transplantation. Trasnplantation. 2001; 71:674-677.
69. Hahn AB, Kasten-Jolly JC, Constantino DM, Graffunder E, Singh TP, Conti DJ. TNF-alpha, IL-6, IFN-gamma, and IL-10 gene expression polymorphisms and the Il-4 receptor alpha-chain variant Q576R: effects on renal allograf toutcome. Tansplantation. 2001; 72: 660-665.
70. McShane P. Association of polymorphisms in the human interferon-gamma and IL-10 gene with acute and chronic kidney transplant outcome. Transplantation. 2002; 73: 1682.
71. Llorente L, Zou W, Levy Y, et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med. 1995; 181:839-844.
72. Llorente L, Richaud-patin Y, Couderc J, et al. Dysregulation of interleukin-10 production in relatives of patients with systemic lupus erythematosus. Arthritis Rheum. 1997; 40:1429-1435.
73. Eskdale J, Wordsworth P, Bowman S, Field M, Gallagher G. Association between polymorphisms at the human IL-10 locus and systemic lupus erythematosus (published erratum appears in Tissue Antigens 50:699). Tissue Antigens. 1997; 49:635-639.
74. Lazarus M, Hajeer AH, Turner D, et al. Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol. 1997; 24:2314-2317.
75. Gonzalez-Amaro R, Portales-Perez D, Baranda L, et al. Role of IL-10 in the abnormalities of early cell activation events of lymphocytes from patients with systemic lupus erythematosus. J Autoimmun. 1998; 11:395-402.
76. Rood MJ, Keijsers V, van der Linden MW, et al. Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann Rheum Dis. 1999; 58:85-89.
77. Asadullah K, Eskdale J, Wiese A, Gallagher G, Friedrich M, Sterry W. Interleukin-10 promotor polymorphism in psoriasis. J Invest Dermatol. 2001; 116:975-978.
78. Hensen P, Asadullah K, Windemuth C, et al. Interleukin-10 Promoter Polymorphism IL10.G and Familar Early Onset Psoriasis. Br J Dermatol. 2003; 149:381-385
79. Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol. 1995; 15:121-129.
80. De Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991; 174:1209-1220.
81. De Waal Malefyt R, Haanen J, Spits H et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991; 174:915-924.
82. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O´Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991; 147:3815-3822.
83. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993; 75:263-274.
84. Powrie F, Leach M, Mauze S, Caddle L, Coffman R. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol. 1993; 5:1461-1471.
85. Herfarth H, Mohanty S, Rath H, Tonkonogy S, Sartor R. Interleukin 10 suppresses experimental chronic, granulomatous inflammation induced by bacterial cell wall polymers. Gut. 1996; 39:836-845.
86. Barbara G, Xing Z, Hogaboam CM, Gauldie J, Collins SM. Interleukin 10 gene transfer prevents experimental colitis in rats. Gut. 2000; 46:344-349.
87. Rott O, Fleischer B, Cash E. Interleukin-10 prevents experimental allergic encephalomyelitis in rats. Eur J Immunol. 1994; 24:1434-1440.
88. Van Laethem JL, Marchant A, Delvaux A, et al. Interleukin 10 prevents necrosis in murine experimental acute pancreatitis. Gastroenterology. 1995; 108:1917-1922.
89. Pennline KJ, Roque-Gaffney E, Monahan M. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin Immunol Immunopathol. 1994; 71:169-175.
90. Gerard C, Bruyns C, Marchant A, et al. Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med. 1993; 177:547.
91. Persson S, Mikulowska A, Narula S, O'Garra A, Holmdahl R. Interleukin-10 suppresses the development of collagen type II-induced arthritis and ameliorates sustained arthritis in rats. Scand J Immunol. 1996; 44:607-614.
92. Tanaka Y, Otsuka T, Hotokebuchi T, et al. Effect of IL-10 on collagen-induced arthritis in mice. Inflamm Res. 1996; 45:283-288.
93. Croxford JL, Feldmann M, Chernajovsky Y, Baker D. Different therapeutic outcomes in experimental allergic encephalomyelitis dependent upon the mode of delivery of IL-10. J Immunol. 2001; 166: 4124-4130.
94. Broberg E, Setala N, Roytta M et al. Expression of IL-4 but not of IL-10 from replicative herpes virus type 1 viral vector precludes experimental allergic encephalomyelitis. Gene Ther. 2001; 8: 769-777.
95. Cua DJ, Hutchins B, LaFace DM, Stohlman SA, Coffmann RL. Central nervous system expression of IL-10 inhibits autoimmune encephamyelitis. J Immunol. 2001; 166: 602-608.
96. Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med. 1994; 179:305-310.
97. Ayala A, Lehmann DL, Herdon CD, Chaudry IH. Mechanism of enhanced susceptibility to sepsis following hemorrage. IL-10 suppression of T cell response is mediated by eicosanoid-induced IL-4 release. Arch Surg. 1994; 129: 1172-1178.
98. Kobayashi H, Kobayashi M, Herndon DN, Pollard RB, Suzuki F. Susceptibility of thermally injured mice to cytomegalovirus infection. Burns. 2001; 27: 675-680.
99. Song GY, Chung CS, Chaudry IH, Ayala A. What is the role of IL-10 in polymicrobial sepsis: anti-inflammatory agent or immunosuppressant? Surgery. 1999; 126: 378-383.
100. Chmiel JF, Konstan MW, Saadane A et al. Prolonged inflammatory response to acute Pseudomonas challenge in IL-10 knockout mice. Am J Respir Crit Care. 2002; 165: 1176-1181.
101. Puluti M, von Hunolstein C, Verwaerde C, Bistoni F, Orefici G, Tissi L. Regulatory role of IL-10 in experimental group B streptococcal arthritis. Infect Immun. 2002; 70: 2862-2868.
102. Schopf LR, Hoffmann KF, Cheever AW, Urban JF, Wynn TA. IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. J Immunol. 2002; 168: 2383-2392.
103. Sabat R, Asadullah K. Interleukin-10 in cancer immunity, In: Cancer Immune Therapy: Experiences and Future Stratgies Eds: G. Stuhler and P. Walden, Wiley-VCH, Weinheim, 2002.
104. Chernoff AE, Granowitz EV, Shapiro L et al. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995; 154:5492-5499.
105. Fuchs AC, Granowitz EV, Shapiro L, et al. Clinical, hematologic, and immunologic effects of interleukin-10 in humans. J Clin Immunol. 1996; 16:291-303.
106. Huhn RD, Pennline K, Radwanski E, Clarke L, Sabo R, Cutler DL. Effects of single intravenous doses of recombinant human interleukin-10 on subsets of circulating leukocytes in humans. Immunopharmacology. 1999; 41:109-117.
107. Huhn RD, Radwanski E, Gallo J, Affrime MB, Sabo R, Gonyo G, Monge A and Cutler DL Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers. Clin Pharmacol Ther. 1997; 62:171-180.
108. Andersen SR, Lambrecht LJ, Swan SK et al. Disposition of recombinant human interleukin-10 in subjects with various degrees of renal function. J Clin Pharmacol. 1999; 39:1015-1020.
109. Radwanski E, Chakraborty A, Van Wart S, et al. Pharmacokinetics and leukocyte responses of recombinant human interleukin-10. Pharm Res. 1998; 15:1895-1901.
110. Gorski JC, Hall SD, Becker P, Affrime MB, Cutler DL, Haehner-Daniels B In vivo effects of interleukin-10 on human cytochrome P450 activity. Clin Pharmacol Ther. 2000; 67:32-43.
111. Pajkrt D, van der Poll T, Levi M, et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood. 1997; 89:2701-2705.
112. Wissing KM, Morelon E, Legendre C, et al. A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy. Transplantation. 1997; 64: 999-1006.
113. Cooper PJ, Fekade D, Remick DG, Grint P, Wherry J, Griffin GE. Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction. J Infect Dis. 2000; 181:203-209.
114. Van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin-10 in steroid refractory Crohn´s disease. Chron´s Disease Study Group. Gastroenterology. 1997; 113:383-389.
115. Fedorak RN, Gangl A, Elson CO, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology. 2000; 119:1473-1482.
116. Schreiber S, Fedorak RN, Nielsen OH, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology. 2000; 119:1461-1472.
117. Colombel JF, Rutgeerts P, Malchow H et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease. Gut. 2001; 49:42-46.
118. Keystone E, Wherry J, Grint P. IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am. 1998; 24:629-639.
119. Narula K. Interleukin 10 - A therapeutic cytokine for chronic inflammatory diseases. Curr Opin Anti-Inflammatory Immunomodulatory Invest Drugs. 2000; 2:307-313.
120. Asadullah K, Sterry W, Stephanek K et al. IL-10 is a key cytokine in psoriasis: Proof of principle by IL-10 therapy - a new therapeutic approach. J Clin Invest. 1998; 101:783-794.
121. Reich K, Bruck M, Grafe A, Vente C, Neumann C, Garbe C. Treatment of psoriasis with interleukin-10 letter . J Invest Dermatol. 1998; 111:1235-1236.
122. Reich K, Garbe C, Blaschke V, et al. Response of Psoriasis to Interleukin-10 is Associated with Suppression of Cutaneous Type 1 Inflammation, Downregulation of the Epidermal Interleukin-8/CXCR2 Pathway and Normalization of Keratinocyte Maturation. J Invest Dermatol. 2001; 116:319-329.
123. Kimball AB, Kawamura T, Tejura K, et al. Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Arch Dermatol. 2002; 138:1341-1346.
124. McInnes IB, Illei GG, Danning CL, et al. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol. 2001; 167:4075-4082.
125. Friedrich M, Döcke WD, Klein A, et al. Immunomodulation by IL-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in psoriasis. J Invest Dermatol. 2002; 118:672-677.
126. Angel JB, Jacobsen MA, Skolnik PR et al. A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects. AIDS. 2000; 14:2503-2508.
127. Boyer N, Marcellin P. Pathogenesis, diagnosis and management of hepatitis C. J Hepatol. 2000; 32: 98-112.
128. Dharancy S, Canva V, Gambiez L, Paris JC, Descreumaux P. Hepatic deficiency of IL-10 in chronic hepatitis C. Gastroenterology. 2000; 119: 1411-1412.
129. Nelson DR, Lauwers GY, Lau JY, Davis GL. IL-10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial of interferon nonresponders. Gastroenterology. 2000; 118: 655-660.
130. Schuppan D, Hahn EG. IL-10: the magic bullet for liver fibrosis? Gastroenterology. 2000; 119: 1412-1414.
131. Llorente L, Garcia-Padilla C, Richaud-Patin Y, et al. Treatment of systemic lupus erythematosus with an anti-IL-10 monoclonal antibody: clinical and biological aspects. Presentation at the 2nd international IL-10 workshop, May 27-29, 1999; Milano.
132. de Vries JE, de Waal Malefyt R, Yssel H, Roncarolo MG, Spits H. Do human TH1 and TH2 CD4+ clones exist? Res Immunol. 1991; 142(1):59-63.
133. Scheffold A, Huhn J, Hofer T. Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-) two to tango. Eur J Immunol. 2005; 35(5):1336-1341.
134. Pistoia V. Production of cytokines by human B cells in health and disease. Immunol Today 1997; 18: 343-350.
135. Nakajima H, Gleich GJ, Kita H. Constitutive production of IL-4 and IL-10 and stimulated production of IL-8 by normal peripheral blood eosinophils. J Immunol 1996; 156:4859-4866.
136. Lin TJ, Befus AD. Differential regulation of mast cell function by IL-10 and stem cell factor. J Immunol 1997; 159:4015-4023.
137. Enk AH, Katz SI. Identification and induction of keratinocyte-derived IL-10. J Immunol 1992; 149:92-95.
138. Teunissen MB, Koomen CW, Jansen J, et al. In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein. Clin Exp Immunol 1997; 107:213-223.
139. Enk AH, Angeloni VL, Udey MC, Katz SI. Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. J Immunol 1993; 151:2390-2398.
140. Mitra RS, Judge TA, Nestle FO, Turka LA, Nickoloff BJ. Psoriatic skin-derived dendritic cell function is inhibited by exogenous IL 10. Differential modulation of B7 1 (CD80) and B7 2 (CD86) expression. J Immunol 1995; 154:2668-2677.
141. D'Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 1993; 178:1041-1048.
142. Hart PH, Hunt EK, Bonder CS, Watson CJ, Finlay-Jones JJ. Regulation of surface and soluble TNF receptor expression on human monocytes and synovial fluid macrophages by IL-4 and IL-10. J Immunol 1996; 157:3672-3680.
143. Jenkins JK, Malyak M, Arend WP. The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophiles. Lymphokine Cytokine Res1994; 13:47-54.
144. Takanaski S, Nonaka R, Xing Z, O'Byrne P, Dolovich J, Jordana M. Interleukin 10 inhibits lipopolysaccharide-induced survival and cytokine production by human peripheral blood eosinophils. J Exp Med 1994; 180:711-715.
145. Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S. Interleukin-10 upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 1994; 179:1695-1699.
146. Thompson-Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, Rennick DM. Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med 1991; 173:507-510.
147. Matsuda M, Salazar F, Petersson M, et al. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med 1994; 180:2371-2376.
148. Uejima Y, Takahashi K, Komoriya K, Kurozumi S, Ochs HD. Effect of interleukin-10 on anti-CD40- and interleukin-4-induced immunoglobulin E production by human lymphocytes. Int Arch Allergy Immunol 1996; 110:225-232.
149. Bécherel PA, Le Goff L, Ktorza S, et al. Interleukin-10 inhibits IgE-mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes. Eur J Immunol 1995; 25:2992-2995.
150. Seifert M, Gruenberg BH, Sabat R, et al. Keratinocyte unresponsiveness towards interleukin-10: lack of specific binding due to deficient IL-10 receptor 1 expression.. 2002
151. Seifert M, Sterry W, Effenberger E, et al. The antipsoriatic activity of IL-10 is rather caused by effects on peripheral blood cells than by direct effect on human keratinocytes. Arch Derm Res 2000; 292:164-172.
152. Vora M, Romero LI, Karasek MA. Interleukin-10 induces E-selectin on small and large blood vessel endothelial cells. J Exp Med 1996; 184:821-829.
153. Asadullah K, Döcke WD, Ebeling M, et al. Interleukin-10 treatment of psoriasis - clinical results of a Phase II trial. Arch Dermatol 1999; 135:187-192.
154. Kimball AB, Kawamura T, Tejura K, et al. Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Arch Dermatol. 2002; 138:1341-1346.
155. Asadullah K, Sterry W, Trefzer U. Cytokine therapy in dermatology. Exp Dermatol 2002; 11:97-106.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
-->