Determinação da neopterina e de defesas antioxidantes na asma de evolução arrastada

 

The evaluation of neopterin and antioxidants in long lasting asthma

 

A Mota Pinto ¹

A Todo-Bom ²

S Vale Pereira ³

V Alves ⁴

M Santos Rosa ⁵

 

Resumo

A asma é uma doença caracterizada por uma resposta imuno-inflamatória a diferentes estímulos desencadeantes. A neopterina (NPT) é sintetizada por macrófagos após estimulação por interferon-ã produzido por linfócitos T e demonstrou-se ter capacidade de ampliar o potencial oxidativo das espécies reactivas de oxigénio. A determinação de NPT é útil para monitorizar a activação imunológica celular dos linfócitos Th1.

Este estudo tem como objectivo analisar a NPT na asma de longa evolução enquanto marcador de um ambiente citocínico do tipo Th1. Avaliaram-se, no grupo de asmáticos e no grupo-controlo, os indicadores de alergia (IgE, eosinófilos e testes cutâneos de alergia por picada). Determinou-se também a NPT, a proteína C reactiva (PCR), total antioxidant status (TAS) e superoxide dismutase enzyme (SOD). Seleccionaram-se idosos com mais de 65 anos. Grupo-controlo – 41 indivíduos saudáveis (79±7 anos); grupo de asmáticos – 64 indivíduos (72±5 anos).

Os valores dos eosinófilos e de IgE estavam estatisticamente aumentados e os de NPT reduzidos entre asmáticos alérgicos e não alérgicos, respectivamente (5,42±4,7vs 2,8±2,8; p<,04), (493,2±549,8 vs 85,3±194,4UI/ml; p=,000), (2,4±2,8 vs 4,0±4,7ng/ml).

O estudo das defesas antioxidantes (TAS, SOD) revelou no grupo-controlo valores significativamente superiores aos do dos asmáticos (p=,000) tanto de TAS (0,84±0,14/0,86±0,11vs 0.91±0,10mM) como de SOD (584,8±108,7/595,6±235,9 vs 822,9±179,5).

Os resultados sugerem o envolvimento dos macrófagos na patogénese da asma. O défice das defesas antioxidantes é um factor de agravamento desta doença. O aumento da NPT na asma não alérgica consolida estas afirmações, sendo a determinação deste parâmetro susceptível de ser incluída no painel de estudos analíticos que permitem distinguir a asma alérgica da asma não alérgica.

Palavras-chave: Neopterina, envelhecimento, TAS, SOD.

 

Abstract

Asthma is a condition characterised by a chronic immunoinflammatory response to different triggers. Neopterin (NPT) is synthesised by human macrophages upon stimulation with interferon-ã and is also capable of enhancing the oxidative potential of reactive oxygen species. NPT is useful for the monitoring of cell-mediated (Th1-type) immune activation.

This study analysed the behaviour of NPT in long lasting asthma, considering its role as a marker of Th1 environment. Allergic parameters (skin prick tests, Immunoglobin E (IgE), and eosinophil count) and NPT were evaluated in an asthmatic group and in a control group. We also analysed the C Reactive Protein (CRP) concentration, Total Antioxidant Status (TAS) and Superoxide Dismutase Enzyme (SOD) in both groups. A group of individuals aged over 65 years old was selected. It included 64 asthmatic patients (72±5 years) and 41 healthy individuals (79±7 years). Blood cell counts showed statistically different median values of eosinophils (5.42±4.7 vs 2.8±2.8;p<.04), IgE (493.2±549.8 vs 85.3±194.4UI/ml; p=.000) and NPT was non-statistically decreased (2.4±2.8 vs 4.0±4.7ng/ml) in allergic asthmatic patients when compared with non-allergic asthmatic patients. Both allergic and non-allergic asthmatic patients presented a statistically significant decreased expression of TAS (0.84±0.14/0.86±0.11 vs 0.91±0.10 mM) and SOD (584.8±108.7/595.6±235.9 vs 822.9±179.5) when compared with normal control subjects. Our results suggest macrophage involvement in asthma pathogenesis. The deficit in antioxidant defence impacts negatively on this disease. The increase of NPT values in non-allergic asthma consolidates these affirmations and mapping this parameter should be part of the work of an analytical study panel as it may lead to allergic asthma being distinguished from nonallergic asthma.

Key-words: Neopterin, asthma, aging, TAS, SOD.

 

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Bibliografia/Bibliography

1. New NHLBI guidelines for the diagnosis and management of asthma. National Heart, Lung and Blood Institute. Lippincott Health Promot Lett 1997; 2(7):1, 8-9.        [ Links ]

2. Kupczyk M. Long-term deterioration of lung function in asthmatic outpatients. Respiration 2004;71:233-40.

3. Vignola AM, Scichilone N, Bousquet J, Bonsignore G, Bellia V. Aging and asthma:pathophysiological mechanisms. Allergy 2003;58:165-175.

4. Braman S, Kaemmerlen J, Davis S. Asthma in the Elderly. Am Rev Respir Dis 1991;143:336-340.

5. Ledochowski M, Murr C, Widner B, Fuchs D. Inverse Relationship between Neopterin and Immunoglobulin E. Clinical Immunol 2001;98(1):104-108.

6. Kaski JC. Neopterin – A Forgotten Biomarker. JACC 2003;42(6):1140–6.

7. Mildvan D, Spritzler J, Grossberg SE, Fahey JL, Johnston DM, Schock BR, Kagan J. Serum Neopterin, an Immune Activation Marker, Independently Predicts Disease Progression in Advanced HIV-1 Infection. Clin Infect Dis 2005;40:853-8.

8. Khodr B, Khalil Z. Modulation of inflammation by reactive oxygen species: implications for aging and tissue repair. Free Rad Biol & Med 2001;30:1-8.

9. Widner CB, Wirleitnerand B, Fuchs D. Neopterin as a Marker for Immune System Activation. Current Drug Metabolism 2002;3:175-187.

10. Hoffman G, Wirleitner B, Fuchs D. Potential role of immune system activation-associated production of neopterin derivates in humans. Inflamm Res 2003;52(8):313-21.

11. Murra C, Schroecksnadela K, Winklera C, Ledochowskic M, Fuchsa D. Antioxidants may increase the probability of developing allergic diseases and asthma. Medical Hypotheses 2005;64:973-977.

12. Frick B, Schroecksnadel K, Neurauter G, Leblhuber F, Fuchsa D. Increasing production of homocysteine and neopterin and degradation of tryptophan with older age. Clin Biochem 2004;37:684-687.

13. Fahey JL, Schnelle JF, Boscardin J, Thomas JK, Gorre ME, Aziz N, Sadeghi H, Nishanian P. Distinct categories of immunologic changes in frail elderly. Mech Ageing Develop 2000;115:1-20.

14. Ledochowski M, Murr C, Jäger M, Fuchs D. Dehydroepiandrosterone, ageing and immune activation. Exp Gerontol 2001;36:1739-1747.

15. Knudson R, Slavin R, Lebowitz M, Burrows B. The maximum expiratory flow volume curve: normal standards, variability and effects of age. Am Rev Respir Dis 1976;113:587-600.

16. Laich A, Neurauter G, Wirleitner B, Fuchs D. Degradation of serum neopterin during daylight exposure. Clin Chim Acta 2002;322:175-178.

17. McCord JM, Fridovich I. The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem 1968; 243(21):5753-60.

18. Flohe L, Otting F. Superoxide dismutase assays. Methods Enzymol 1984;105:93-104.

19. Renwick DS, Connolly MJ. Persistence of atopic effects on airway calibre and bronchial responsiveness in older adults. Age and Ageing 1997;26:435-440.

20. Huss K, Naumann PL, Mason PJ, et al. Asthma severety, atopic status, allergen exposure, and quality of life in elderly persons. Ann Allergy Asthma Immunol 2001;86:524-30.

21. Scichilone N, Messina M, Battaglia S, Catalano F, Bellia V. Airway hyperresponsiveness in the elderly: prevalence and clinical implications. Eur Respir J 2005; 25:364-375.

22. Menz G, De Sousa JJ, Rothe T, Schmitz-Schumann M, Virchow C. Neopterin in phases of exacerbation of bronchial asthma and in experimental asthma conditions. Pneumologie 1990;44: 232-3.

23. Murr C, Hainz U, Asch E, Berger P, Jenewein B, Saurwein-Teissl M, et al. Association of increased neopterin production with decreased humoral immunity in the elderly. Exp Gerontol 2003;38:583-587.

24. Gruber A, Murr C, Wirleitner B, Werner-Felmayer G, Fuchs D. Histamine suppresses neopterin production in the human myelomonocytoma cell line THP-1. Immunology Letters 2000;72:133-136.

25. Todo Bom A, Proença T, et al. O Sistema Antioxidante na Asma Brônquica: Condicionalismos do Processo de Envelhecimento. Rev Port Imunoalergologia 2003;XI:17-29.

26. Smith L, Shamsuddin M, Sporn P, Denenberg M, Anderson J. Reduced superoxide dismutase in lung cells of patients with asthma. Free Radical Biology & Medicine 1997;95:1301-07.

27. Comhair S, Bhatena P, Dweik R, Kavuru M, Erurum S. Rapid loss of superoxide dismutase activity during antigen induced asthmatic response. Lancet 2000;355:624-24.

 

¹ Professora Associada da Faculdade de Medicina da Universidade de Coimbra. Directora do Instituto de Patologia Geral da Faculdade de Medicina de Coimbra / Associate Professor, Coimbra University Medical School. Director, General Pathology Unit, Coimbra University Medical School.

² Assistente Hospitalar Graduada de Imunoalergologia dos Hospitais da Universidade de Coimbra / Hospital Assistant, Graduate in Allergy and Clinical Immunology, Coimbra University Hospitals.

³ Mestre em Biologia Celular. Técnico Superior de 2.ª Classe do Instituto de Patologia Geral da Faculdade de Medicina da Universidade de Coimbra / MSc in Cellular Biology. Senior Technician (Grade II), General Pathology Unit, Coimbra University Medical School.

⁴ Licenciada em Bioquímica. Assistente da Disciplina Imunologia e Investigadora do Instituto de Imunologia da Faculdade de Medicina da Universidade de Coimbra / BSc in Biochemistry, Assistant, Clinical Immunology, Researcher in Clinical Immunology, Coimbra University Medical School.

⁵ Professor Catedrático da Faculdade de Medicina da Universidade de Coimbra. Director do Instituto de Imunologia da Faculdade de Medicina de Coimbra / Cathedratic Professor, Coimbra University Medical School. Director, Clinical Immunology Unit, Coimbra University Medical School.

 

Instituto de Patologia Geral

(Directora: Profª. Doutora Anabela Mota Pinto)

Faculdade de Medicina da Universidade de Coimbra

Rua Larga

3004-504 Coimbra

 

Departamento de Imunoalergologia

(Director: Dr. Celso Chieira)

Hospitais da Universidade de Coimbra

Praceta Mota Pinto

3000 Coimbra

 

Instituto de Imunologia

(Director: Prof. Doutor Manuel Santos Rosa)

Faculdade de Medicina da Universidade de Coimbra

Rua Larga

3004-504 Coimbra

 

Recebido para publicação/received for publication: 06.07.14

Aceite para publicação/accepted for publication: 06.08.29