desviadas para a esquerda, ao contnirio dos individuossaudaveis que tern curvas desviadas para a direita eachatadas). 0 aumento da susceptibilidade dos branquiosa estimulos farmacologicos nos asmaticos tern sidoatribuido a presenya de inflamayao branquica. Existemdivers os argumentos para fundamentar esta hipotese,nomeadamente 0 efeito dos anti-inflamatorios esteroidesque desviam a curva de dose-resposta para a dire ita, 14

aumentando a PDIPC e reduzindo 0 grau de obstruyaobranquica maxima ou do plateau induzidos por estimulosfarmacologicosY, 16 Por outro lado, Mackleml7• 18 pas ahipotese de que a existencia de inflamayao das vias aerascom presenya de edema, determinando a reduyao dolumen (diametro interno) amplificaria 0 efeito doencurtamento do musculo liso branquico e que, por outrolado, alterando 0 diametro externo diminuiria as foryasde tracyao elastica aplicadas sobre a parede e,consequentemente, a carga contra a qual 0 musculo lisose contrai levando a obstruyao excessiva. 0 edemaperibranquico podeni estar na origem da hiperinsuflayaopulmonar cronic a do asmMico atraves do papel quedesempenha na reduyao da tracyao elastica do pulmaopor perda da interdependencia entre parede branquica eparenquima pulmonar.

1. Robbins RA, Barnes PJ, Springall DR, et al. Expression ofinducible nitric oxide synthase in human bronchial epithelial cells.Biochem Biophys Res Commun 1994; 203: 209-218.

2. Dinh-Xuan AT. Roles du NO en Physiopathologie cardiovas-culaire et respiratoire. Arch Intern de Physiol, Bioch et Biophys1994; 102: A3-A9.

3. Kharitonov SA, Yates D, Robbins RA et al. Increased nitric oxidein exhaled air of asthmatic patients. Lancet 1994; 343: 146-147.

4. Barnes PJ, Liew FY. Nitridc oxide and asthmatic inflammation.Immunol Today 1995; 16: 128-130.

5. Kharitonov S, Alving K, Barnes PJ. Exhaled and nasal nitricoxide measurements: recommendations. The European RespiratorySociety Task Force. Eur Resp J 1997 Jul; 10(7): 1683-1693.

6. Hamann KJ. Eosinophil mediators in: Asthma and Rhinitis ed.Busse WW e Holgate ST 1995 Blackwell Scientific Publications.

7. Kuo H-P, Yu T-R, Yu C- T. Hypodense eosinophil numberrelates to clinical severity, airway responsiveness and responseto inhaled corticosteroids in asthmatic patients. Eur Respir J 1994;7: 1452-1459.

8. Gleich GJ, Frigas E, Loegering DA, Wassom DL, Stein mullerD. Cytotoxic properties of the eosinophil major basic protein.J Immunol1979; 123: 2925-7.

9. Venge P, Dahl R, Fredens K, Peterson CG. Epithelial injuryby human eosinophils. Am Rev Respir Dis 1988; 138: 554-557.

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Existem interacyoes funcionais e uma linguagemcomum entre 0 sistema imune (SI) e neuroendocrino (NE).As celulas do SI produzem hormonas e neuropeptidos eas do NE citoquinas. Estes sistemas interagem paramanutenyao da homeostase. Existem receptores em ambosos sistemas.

A estimulayao do sistema imune aumenta a actividadedo eixo Hipotalamo - pituitaaria (HPA), fenomenomediado por citoquinas.

Por exemplo, in vitro esta document ado urn papel dasubstancia P (SP) na produyao de IL-2 enquanto 0 VIPtern efeito oposto. A IL-2 estimula a produyao de oxidonitrico. 0 oxido nitrico diminui ACTH por inibiyao delibertayao de CRF. Em termos gerais restringe a respostado HPA as citoquinas circulantes. A IL-5, 9 e TGF~regulam a diferenciayao neuronal.

Atraves de modelos de granulomas parasitariosmostrou-se que os eosinOfilos segreram SP e VIP queactuam em celulas T CD4+, com a SP a estimular IFNy.

VIP e CGRP inibem a prolifera9ao de celulas T, maspor diferentes mecanismos - ao contnlrio do VIP, 0 CGRPnao afecta os niveis de IL-2, mas eleva os niveis de AMPc,aC9ao potenciada pela teofilina.

Outros autores encontraram inibi9ao do CGRP emcelulas Thl produtoras de IL-2,juntamente com inibi9aode TNFa e IFNy.

o CGRP tern actividade como neurotransmissor,neuromodulador, hormona local e factor tr6fico,resultando em altera90es da actividade neuronal, aC90esno metabolismo e altera90es da expressao de genes.

A selec9ao de report6rio T intratimico e influenciadopor secre9ao local de glucoicortic6ides, ACTH, CRH, bemcomo por CGRP atraves dos receptores identificadosno timo. Existem receptores identificados no ba90.Os linf6citos perifericos nao respondem ao CGRP.o CGRP age atraves da eleva9ao de AMPc tendo portantourn efeito inibidor. Actividade contnlria tern a dehidroe-piandrosterona (DHEA).

IL-l~, IL-6 e TNF a sao considerados mediadores paraactiva9ao da resposta do eixo hipotalamo-hipofisario-suprarenal (ao contrario do 6xido nitrico), comhipersensibilidade adrenocortical ao ACTH. Actuamlibertando CRH pelo hipotalamo, que leva a liberta9aode ACTH pela pituitaria, libertando glucocortic6ides eandrogeneos (ex: DHEAS) pela supra-renal.

A DHEAS circula como prohormona inactiva,activando-se nos orgaos alvo perifericos - DHEA -- actuando nos receptores celula T, estimulando as Thl.A DHEA tern actividade inversa ados glucocortic6ides,estimulando Thl, dado que os glucocortic6ides estimulamdiferencia9ao para Th2.

Para alem disso, em termos gerais os glucocortic6idesinibem a prolifera9ao de linf6citos e a DHEA estimula aprolifera9ao de linf6citos.

o balance Th l/Th2 no tecido linf6ide do rata einfluenciado pela actividade da DHEA sulfatase (enzimaque transforma DHEAS em DHEA).

Outro mecanismo de estimula9ao para a pituitarialibertar ACTH e 0 stress levando este tambem a altera9aodo balan90 Thl/Th2 em favor de Th2, devido a quedados niveis de DHEAS (0 stress estimula secre9ao deglucocortic6ides e suspensao de DHEAS) e consequen-temente de DHEA, com ausencia de activa9ao de Thl edesvio para Th2.

Esta documentado em ratos idosos que a suplemen-ta9ao com DHEA aumenta a produ9ao de IL-2 e IFNycom diminui9ao de citoquinas de perfil Th2. No homemidoso a suplementa9ao com DHEA teve efeitossemelhantes. A suplementa9ao com DHEA tern assimefeitos imunomoduladores com importancia a variosniveis, por exemplo na SIDA.

Em grupo etario pediatrico nao encontramosaltera90es dos valores de DHEA e DHEAS em at6picose nao at6picos, nao parecendo assim neste grupo etariohaver contribui9ao desta via de regula9ao imuno--endocrina para 0 perfil Thl/Th2.

Existem autores que sugerem que a Asma poderia serdevida a mau funcionamento da interac9ao entre 0 SI eneuronal. A estimula9ao Ag afecta a despolariza9aoneuronal. A estimula9ao neuronal afecta 0 crescimento efun9ao das celulas inflamat6rias. Outros provaram que 0humor influencia a magnitude da reac9ao alergica deforma indirectamente proporcional.

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