Mediadores pró-inflamatórios e antinflamatórios na sepse neonatal: associação entre homeostase e evolução clínica
DOI:
https://doi.org/10.7322/jhgd.19875Palavras-chave:
Recém-nascido, Sepse, Mediadores pró-inflamatórios (TNF-±, IL-², IL-6), Mediadores antinflamatórios (IL-10 e IL-1Ra), Relação IL-6/IL-1RaResumo
OBJETIVO: avaliar a utilidade de citocinas pró-inflamatórias (TNF-±, IL-1² e IL-6) e de citocinas antinflamatórias (IL-10 e IL-1Ra) no diagnóstico da sepse neonatal, e verificar se a homeostase entre estes mediadores poderia ser determinante para a evolução clínica da doença. MÉTODO: coorte prospectiva compreendendo 31 recém-nascidos (RN) com diagnóstico de sepse neonatal, classificados em dois grupos: sepse e sepse grave, com evolução complicada (choque, falência múltipla de órgãos, óbito). Os níveis séricos de TNF-±; IL-1²; IL-6; IL-10 e IL-1Ra foram mensurados nos dias 0 (diagnóstico), 3 e 7 (evolutivos). Foram calculadas as médias, desvios-padrão, medianas, e valores mínimos e máximos para cada um dos mediadores. Foram construídos gráficos dos perfis individuais dos pacientes, e o perfil médio dos dois grupos contendo os erros-padrão. Para o tratamento estatístico dos dados oriundos da avaliação das concentrações de citocinas ao longo do tempo, foi utilizado o teste ANOVA com medidas repetidas. Para todas as análises realizadas foi adotado nível de significância de 5%. RESULTADOS: no grupo de recém-nascidos com sepse e boa evolução, os níveis séricos de TNF-±; IL-1² e Il-10 se apresentaram próximos aos valores mínimos detectáveis pelo método, e nos RN com sepse grave, esses níveis foram estatisticamente superiores (p;1) e da resposta antiinflamatória nos dia 3 e 7 de evolução (razão ;1) e somente no dia 7, houve predomínio da ação antiinflamatória (razão ;1, com inversão nos dias 3 e 7). A persistência de predomínio das citocinas pró-inflamatórias em relação às antiinflamatórias no terceiro dia após o diagnóstico está correlacionada à evolução clínica desfavorável.Downloads
Referências
Zupan J, Aahman E. Perinatal mortality for the year 2000: estimates developed by WHO. Geneva: World Health Organization; 2005.
Lawn JE, Cousens S, Zupan J, for the Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005;365:891-900.
Cunneen J, Cartwright M. The puzzle of sepsis. Fitting the pieces of the inflammatory Response with treatment. AACN Clinical Issues. 2004;15:18-44.
Hageman JR, Caplan MS. Introduction the structure and function of inflammatory mediators for clinician. Clin Perinatol. 1995;22:251-61.
Oberholzer A, Oberholzer C, Moldawer LL. Cytokine signaling: regulation of the immune response in normal and critically ill states. Crit Care Med. 2000;28:3-12.
Netea MG, Van Der Meer JWM, Van Deuren M, Kullberg BJ. Pro inflammatory cytokines and sepsis syndrome: not enough, or too much of a good thing? Trends Immunol. 2003;24:254-8.
Bellanti JA, Kadlec JV, Escobar-Gutierrez A. Cytokines and the immune response. Pediatr Clin North Am. 1994;41:597-621.
Anderson MR, Blumer JL. Advances in the therapy for sepsis in children. Pediatr Clin North Am. 1997;44:179-205.
Van Deventer SJ, Buller HR, Ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental end toxemia in humans: analysis of cytokine release and coagulation, fibrinolitic and complement pathways. Blood. 1990;76:2520-6.
Ulloa L, Tracey KJ. The ‘ cytokine profile’: a code for sepsis. Trens Mol Med. 2005;11:56-63.
Tracey KJ. The inflammatory reflex. Nature. 2002;420:853-9.
Tracey KJ, Cerami A. Tumor necrosis factor, others cytokines and disease. ANNU Rev CellBio.1993;9:317-43.
Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. ANNU Rev Med. 1994;45:491-503.
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med.2003;348:138-50.
Gea-Banacloche JC, Opal SM, Jorgensen J, Carcillo JA, Sepkowitz KA, Cordonnier C. Sepsis associated with immunosuppressive medications: an evidence-based review. Crit Care Med. 2004;32;(Suppl. 11):S578–S590.
Cohen J. The immune pathogenesis of sepsis. Nature. 2002;420:885-91.
Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987;1:355-7.
Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with sepsis syndrome. Ann Intern Med. 1993;119:771-8.
Küster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, et al. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet. 1998;352:1271-7.
Loise P, Rinne T, Laine S, Hurme M, Kaukinen S. Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis. Acta Anaesthesiol Scand. 2003;47:319-25.
Dinarello CA. Impact of basic research ontomorrow’s medicine. Pro-inflammatory cytokines. Chest. 2000;118:503-8.
Del Vecchio A, Laforgia N, Capasso M, Lolascon A, Latini G. The role of molecular genetics in the pathogenesis and diagnosis of neonatal sepsis. Clin Perinatol. 2004;31:53-67.
Dinarello CA, Wolff SM. The role of interleukin-1 in disease. N Engl J Med. 1993;328:106-13.
Okusawa S, Gelfand JA, Ikejima T, Connolly RJ, Dinarello CA. Interleukin-1 induces a shock like state in rabbits: synergism with tumor necrosis factor and effect of cyclooxygenase inhibition. J Clin Invest. 1988;81:1162-72.
Reyes CS, García-Muñoz Reyes DF, González G, Dominguez C, Domenech E. Role of cytokines(interleukin-1β; 6; 8; tumour necrosis factor-α,and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis. Acta Paediatr; 2003;92:221-7.
Mishra UK, Jacobs SE, Doyle LW, Garland S. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal. 2006;91:F208-F212.
Casey LC. Immunologic response to infection and its role in septic shock. Crit Care Clin. 2000;16:193-213.
Abbas AK, Lichtman AH. Cytokines. In: AbbasAK, Lichtman AH.Cellular and molecular immunology. 5th ed. Philadelphia: Elsevier; 2005. p.243-74.
Ceccon MEJR. Análise do uso das interleucinas 6 e 8 e proteína C reativa para diagnóstico e seguimento terapêutico de recém-nascido com sepse tardia internados na Unidade de Cuidados Intensivos Neonatal[Livre Docência]. São Paulo: Faculdade de Medicina da Universidade de São Paulo; 2002.
Dinarello CA. Pro inflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. Chest.1997;112:321-9.
Ng PC. Diagnostic markers of infection inneonates. Arch Dis Child Fetal Neonatal. 2004;89:F229-F235.
Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late onset sepsis in premature neonates: clinical,hematological and cytokine profile. J Perinat Med. 2003;31:60–8.
Hack CE, De Grott ER, Felt-Bersma RJF, Nuijens JH, Strack Van Schinjndel RJMS, Eerenberg–Belmer AJM, et al. Increased plasm levels of interleukin-6 in sepsis. Blood. 1989;74:1704–10.
Borish LC, Steinke JW. Cytokines and Chemokine. J Allergy Clin Immunol. 2003;111(Suppl.):S460-S475.
Oberholzer A, Oberholzer C, Moldawer LL. Interleukin 10: A complex role in the pathogenesis of sepsis syndromes and its potential as an antiinflamatory drugs Crit Care Med. 2002;30:S58–S63.
Doughty L, Carcillo JA, Kaplan S, Janosky J. The compensatory anti-inflammatory cytokineinterleukin10 response in pediatric sepsis induced multiple organ failure.Chest.1998;113:1625-31.
Howard M, O’garra A, Ishida H, Malefyt RW, Vries J. Biological properties of interleukin 10. J Clin Immunol. 1992;12:239-47.
Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997;112:235-43.
Goldie AS, Fearon KCH, Ross JA, Barclay GR, Jackson RE, Grant IS, Ramsay G, Blyth AS, Howie JC. Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. JAMA. 1995;274:172-7.
Kilpatrick L, Harris MC. Cytokines and the inflammatory response. In: Polin RA, Fox WW. Fetal and neonatal physiology. 2nd ed. Philadelphia: Saunders; 1998. p.1967–79.
Dollner H, Vatten L, Linnebo I, Zanussi GF,Laerdal A, Austgulen R. Inflammatory mediators in umbilical plasma from neonates who develop early onset sepsis. Biol Neonate.2001;80:41-7.
Carrigan SD, Scott G, Tabrizian M. Toward resolving the challenges of sepsis diagnosis. Clinl Chem. 2004;50:1301-14.
Fischer E, Van Zee KJ, Marano MA, Rock CS, Kenney JS, Poutsiaka DD, Dinarello CA, Lowry SF, Moldawer LL. Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood.1992;79:2196-200.
De Bont ESJM, De Leij LHFM, Okken A, Baarsma R, Kimpen JLL. Increased plasmacon centrations of in terleukin-1 receptor antagonist in neonatal sepsis. Pediatr Res.1995;37:626-9.
Van Dissel JY, Van Lange Velde P, Westendorp RG, Kwappenberg K, Frölich M. Anti-inflammatory cytokines profile and mortality in febrile patients . Lancet. 1998;351:950-3.
Taniguchi T, Koido Y, Aiboshi J, Yamashita T, Suzaki S, Kurokawa A. Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med. 1999, jul;27(7):1262-1264.
Downloads
Publicado
Edição
Seção
Licença
CODE OF CONDUCT FOR JOURNAL PUBLISHERS
Publishers who are Committee on Publication Ethics members and who support COPE membership for journal editors should:
- Follow this code, and encourage the editors they work with to follow the COPE Code of Conduct for Journal Edi- tors (http://publicationethics.org/files/u2/New_Code.pdf)
- Ensure the editors and journals they work with are aware of what their membership of COPE provides and en- tails
- Provide reasonable practical support to editors so that they can follow the COPE Code of Conduct for Journal Editors (http://publicationethics.org/files/u2/New_Code.pdf_)
Publishers should:
- Define the relationship between publisher, editor and other parties in a contract
- Respect privacy (for example, for research participants, for authors, for peer reviewers)
- Protect intellectual property and copyright
- Foster editorial independence
Publishers should work with journal editors to:
- Set journal policies appropriately and aim to meet those policies, particularly with respect to:
– Editorial independence
– Research ethics, including confidentiality, consent, and the special requirements for human and animal research
– Authorship
– Transparency and integrity (for example, conflicts of interest, research funding, reporting standards
– Peer review and the role of the editorial team beyond that of the journal editor
– Appeals and complaints
- Communicate journal policies (for example, to authors, readers, peer reviewers)
- Review journal policies periodically, particularly with respect to new recommendations from the COPE
- Code of Conduct for Editors and the COPE Best Practice Guidelines
- Maintain the integrity of the academic record
- Assist the parties (for example, institutions, grant funders, governing bodies) responsible for the investigation of suspected research and publication misconduct and, where possible, facilitate in the resolution of these cases
- Publish corrections, clarifications, and retractions
- Publish content on a timely basis