Other antibiotics, including doxycycline, lymecy-cline, and rifampin, have also been found to inhibit chemotaxis of human neutrophils and to suppress phytohemagglutinin-induced lymphocyte transformation in vitro. Recently, FK506, a macrolide antibiotic, has been shown to inhibit T-cell activation by a mechanism that appears similar to that of cyclosporin A.
Various studies have reported the influence of EM on the host defense mechanisms of patients with DPB, in terms of the changes in lymphocyte subsets increased natural killer cell activity, suppression of oxygen radical products, and suppression of elastase activity. We have previously reported that the BAL fluid supernatant obtained from patients with DPB enhanced superoxide production by neutrophils isolated from healthy volunteers, and that this enhancing effect was reduced to near normal after EM treatment flovent inhalers.
Nagai et al reported a pharmacokinetic study of EM in 11 DPB patients (8 responders and 3 nonresponders) after long-term low-dose administration. They showed that the maximal serum and sputum levels of EM were below the MIC of several clinically pathogenic bacteria often isolated from the sputum of such patients. They also observed no difference between responders and nonresponders in EM absorption. Thus, these studies have led to the conclusion that the therapeutic action of EM in DPB patients is anti-inflammatory rather than antibacterial.
Hopkins et al suggested that the accumulation of neutrophils in the alveoli was a characteristic pathologic finding in bacterial pneumonia, while Martin et al showed that chronic bronchitis patients with chronic cough or with phlegm production had elevated percentages of neutrophils in BAL fluid. In our study, markedly increased numbers of neutrophils were observed in the pretreatment BAL fluid of patients with DPB, consistent with previous reports Neutrophils serve as the first line of host defense by controlling the expansion and dissemination of mi-crobies by killing and removing pathogenic microorganisms