Changes in serum immunomolecules during antibiotic therapy forMycobacterium aviumcomplex lung disease

Abstract

SummaryLittle information is available regarding changes in immune status for patients with Mycobacterium avium complex (MAC) lung disease during antibiotic therapy. Serum immunomolecules from 42 patients with MAC lung disease were assayed comparatively using an array-based system according to (i) patients with MAC lung disease at the time of diagnosis versus healthy controls and (ii) alterations after 12 months of antibiotic therapy in the MAC lung disease group. In addition, cytokine analyses were performed to determine whether cytokine responses were associated specifically with the disease phenotype, treatment outcome and aetiological agent. Notably, the serum concentrations of type 1 cytokine-associated molecules, such as CD40L, interferon (IFN)-γ, interleukin (IL)-8 and IL-23, were decreased significantly in patients at the time of diagnosis, suggesting that these molecules may serve as indicators of host susceptibility to MAC disease. Although the overall serum level of T helper type 1 (Th1)-related molecules, such as CD40L and IFN-γ, was restored after treatment, Th17-related cytokines, such as IL-17 and IL-23, were down-regulated significantly at 12 months posttreatment compared to pretreatment. Furthermore, these cytokine patterns differed among patient subgroups. Decreased serum concentrations of IL-17 and/or IL-23 were associated with failure of sputum conversion, the fibrocavitary disease phenotype and M. intracellulare lung disease. Thus, the reciprocal balance between Th1 and Th17 immunity during antibiotic therapy for MAC lung disease is critical for dictating the treatment response. In conclusion, a low level of Th1-related immunomolecules may perpetuate MAC lung disease, and the serum concentrations of Th17-related cytokines can reflect the treatment outcome, disease phenotype and aetiological agent.

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

“…A hi-dimensional flow analysis between individuals at risk and not at risk of MABS disease revealed immune exhaustion in T cells (CTLA-4) may be playing a role (98). These finding is similar to studies performed in MAC infection (93,95). Interestingly, levels of monokine induced by IFNγ (MIG) and IFNγ induced protein (IP-10) could predict treatment outcome (99).…”

“…Other studies have shown similar results for IFNγ and IL-10 but not for the other cytokines (91)(92)(93)(94). A study of serum cytokine levels comparing newly diagnosed MAC patients showed a significant reduction in IL-6, IL-8, IL-23, IFNγ, and CD40L (95). Longitudinal assessment of Th1 and Th17 cytokines in these patients after 1 year of antibiotic therapy showed that while low Th1 cytokine levels could accelerate infection, Th17 cytokine levels at diagnosis (IL-17 and IL-23) could act as indicators of treatment outcome (sputum conversion vs. failure).…”

Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease

“…HMGB1, a late-phase mediator of inflammation, is induced by early proinflammatory cytokines and triggers the pathological and immunosuppressive effects that accompany the subsequent release of cytokines such as TNF-α, IL-1α, IL-1β, IL-6, and IL-8 during late infection23. In our previous studies, the serum levels of T helper type 1-related cytokines were significantly decreased in patients with NTM lung disease compared with the HC2425. Therefore, the down-regulated levels of HMGB1 in patients with NTM lung disease might be influenced by the decreased levels of proinflammatory cytokines.…”

Immune response assessment of inactivated Newcastle disease virus liposomal-based vaccine

“…3,19,24,25 Recently, the serum levels of certain cytokines have been employed as an indicator for disease diagnosis and prognosis. 26 In humans, cytokines such as IFN-, IL-8, and IL-23 levels in serum have been labeled as immunomolecules and used for determining Th-1 and Th-17 responses against Mycobacterium avium complex diseases, tuberculosis, and papillomavirus infections. [26][27][28] The current work is the first to employ a ChIFN-g measurement, directly in the serum, as a monitoring tool to assess the CMI response in poultry post vaccination.…”

“…26 In humans, cytokines such as IFN-, IL-8, and IL-23 levels in serum have been labeled as immunomolecules and used for determining Th-1 and Th-17 responses against Mycobacterium avium complex diseases, tuberculosis, and papillomavirus infections. [26][27][28] The current work is the first to employ a ChIFN-g measurement, directly in the serum, as a monitoring tool to assess the CMI response in poultry post vaccination. However, the background serum ChIFN-g levels also need to be estimated in chickens exposed to different stressful conditions in the field and in differing bird ages and breeds.…”