Asma e DPOC: duas faces de um mesmo dado? / Asthma and COPD: two faces sides of the same dice?

Os imbricados processos patogênicos da asma e da doença pulmonar obstrutiva crônica (DPOC) têm mecanismos comuns que envolvem redes genéticas, subclasses de linfócitos, diversas citocinas e quimiocinas, gerando comportamento alterado de todas as células estruturais e funcionais do trato respiratório. Uma parte das centenas de genes que vêm sendo implicados na patogenia da asma e da DPOC é comum às duas. Aparentemente, eles formam uma grande rede, e sua ação conjunta está associada às alterações presentes nas duas disfunções respiratórias. Dado que parte da base genética e muitos processos inflamatórios são comuns às duas doenças, pode-se supor que elas componham uma única entidade, que pode se apresentar de diversas formas.

The overlapping pathogenic processes of asthma and chronic obstructive pulmonary disease (COPD) have common mechanisms involving genetic networks, lymphocyte subclasses, several cytokines and chemokines, generating abnormal behavior of all structural and functional cells of the respiratory tract. Part of hundreds of genes implicated in the pathogenesis of asthma and COPD are the same. Apparently, they form a large network and their joint action is associated with several changes in both respiratory disorders. As part of their genetic basis is common and many inflammatory processes are similar in both disorders, we may assume that they form a single entity that may occur in different ways.

Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection

Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.