We herein present a case of Good syndrome complicated by diffuse pulmonary lesions similar to diffuse panbronchiolitis (DPB). A 45-year-old Japanese man was referred to our department due to recurrent lower respiratory tract infections that had started and ameliorated nine months after thymectomy for pure red cell aplasia and myasthenia gravis. Diffuse centrilobular opacities on chest computed tomography and positivity for HLA-B54 were consistent with DPB. Additionally, hypogammaglobulinemia and a marked decrease of B-lymphocytes were observed, and therefore Good syndrome was considered. Combination therapy with azithromycin and clarithromycin alleviated the patient's respiratory symptoms and reduced the exacerbation of chronic bronchitis.
[Show abstract][Hide abstract] ABSTRACT: Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of IkappaBalpha, suggesting the molecular target for EM was not the dissociation of NF-kappaB from IkappaB. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-kappaB DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-kappaB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-kappaB signaling pathway in the downstream of the dissociation from IkappaB, resulting in the inhibition of NF-kappaB.
[Show abstract][Hide abstract] ABSTRACT: Several classes of antibiotics, particularly macrolides and to some extent quinolones, exert modulatory effects on inflammatory cells. With a growing number of experimental and clinical studies being performed, the relevance of the immunomodulatory actions of antibiotics to the therapy of respiratory infections is discussed in the light of recent reports.
Antibiotics, particularly macrolides, exert both stimulatory and inhibitory effects on leukocytes. These effects seem to be related to the activation state of the leukocytes, facilitating bacterial killing as well as the resolution of local inflammation. In community-acquired pneumonia, this may account for the therapeutic benefit of macrolides, even when bacterial eradication is not complete. A variety of effects of macrolides on Pseudomonas aeruginosa, including the inhibition of biofilm matrix, contribute with immunomodulation to the improvement of respiratory function seen with macrolides in cystic fibrosis.
Macrolides can facilitate the killing of microorganisms in acute respiratory infections through the stimulation of neutrophil activation. On long-term administration, anti-inflammatory, T helper type 1 lymphocyte-enhancing and biofilm-thinning actions, among others, make macrolides valid therapeutic options in chronic infectious/inflammatory disorders, even for infections with microorganisms that are not completely eradicated.
Current Opinion in Infectious Diseases 05/2005; 18(2):125-31. DOI:10.1097/01.qco.0000160901.71813.fe · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Summary The macrolide antibiotics are now well known to have anti-inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co-stimulatory molecules and production of cytokines [interleukin (IL)-10, IL-6, interferon (IFN)-gamma, IL-12p40, tumour necrosis factor (TNF)-alpha] of murine bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation. A 15-membered macrolide, AZM, and a 14-membered macrolide, CAM, significantly enhanced the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL-10 and CAM significantly inhibited the production of IL-6 by DCs. However, a 16-membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL-10 and CAM decreased IL-2 productions significantly, when naive T cells derived from spleen were co-cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14-membered and 15-membered, but not 16-membered macrolides play as anti-inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways.
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