Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases

Annual influenza vaccination is strongly recommended for patients with chronic pulmonary diseases, such as bronchial asthma, chronic obstructive pulmonary disease (COPD), and interstitial pulmonary diseases. However, many of these patients regularly receive systemic and/or inhaled corticosteroid therapy, and the impact of corticosteroid therapy on influenza vaccine efficacy and safety is unclear. Patients with chronic pulmonary diseases were enrolled in the study and divided into three groups based on their maintenance therapy: (A) without corticosteroid therapy (17 males, three females; mean age, 72.3 ± 7.9), (B) oral corticosteroid therapy (four males, seven females; mean age, 66.1 ± 10.6), and (C) inhaled corticosteroid therapy (eight males, nine females; mean age, 62.4 ± 16.0). All patients received influenza vaccine, and serum hemagglutination inhibition (HI) antibodies against influenza strains A/H1N1, A/H3N2, and B were measured at baseline (before vaccination) and 4-6 weeks after vaccination. Sufficient antibody titers or significant increases were observed after vaccination compared with titers before vaccination in all three groups. No systemic reactions were reported. Long-term oral/inhaled corticosteroid therapy was not associated with vaccination side effects and did not affect the immune response to the influenza vaccine

Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages

Immunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates sig-nal transducer and activator of transcription (STAT)-3, and subsequently induces the suppres-sor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immu-nomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pre-treated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway

Effect of antibiotic therapy on the inflammatory responses during streptococcal pneumonia in emphysematous mice

Background and objective: Bacterial infection is one of the most important causes of acute exacerbation of respiratory failure in patients with chronic obstructive pulmonary disease (COPD). There were few studies evaluating the effects of early intervention by antibiotic on respiratory bacterial infection in COPD subjects. We investigated the effect of early intervention by respiratory quinolone antibiotic on the systemic inflammatory responses induced by streptococcal pneumonia using a mouse model of experimental emphysema. Methods: Experimental pulmonary emphysema was developed by a single intratracheal instillation of porcine pancreatic elastase in ICR mice. Three weeks later, lethal doses of Streptococcus pneumoniae were intratracheally inoculated, followed by oral administration of 50 mg/kg body weight of Grepafloxacin (GPFX) every day from a day after tracheal inoculation. Results: While all emphysematous mice without GPFX treatment died within 8 days, all emphysematous mice with GPFX treatment survived. Seventy two hrs after infection, serum levels of tumor necrosis factor alpha, chemokine (C-X-C motif) ligand 1, and CXCL2 (Macrophage inflammatory protein-2) in emphysematous mice with antibiotic therapy were significantly lower than those without therapy. Conclusions: Thus, the early intervention using a respiratory quinolone antibiotic prevents emphysematous mice with pneumonia from severe systemic inflammation, and rescues these mice from death. These results suggest that early intervention using a respiratory quinolone may improve the outcome of the exacerbated COPD patients