Mechanisms of Pleural Fibrosis in Empyema: Pleural Macrophage-Mediated Inhibition of Fibroblast Prolifreration

Abstract

Pleural empyema, unless adequately treated with appropriate antibiotics and drainage, progresses to pleural fibrosis. 1 Sahn SA Taryle DA Good Jr., JT Experimental empyema: time course and pathogenesis of pleural fluid acidosis and low pleural fluid glucose. Am Rev Respir Dis. 1979; 61: 120-355 Google Scholar Bacteria-specific antibiotic therapy allows the empyema to resolve without fibrosis. 1 Sahn SA Taryle DA Good Jr., JT Experimental empyema: time course and pathogenesis of pleural fluid acidosis and low pleural fluid glucose. Am Rev Respir Dis. 1979; 61: 120-355 Google Scholar , 2 Antony VB Repine JE Harada RN Good Jr, JT Sahn SA Inflammatory responses in experimental tuberculous pleurisy. Acta Cytol. 1983; 61: 27-355 Google Scholar The mechanisms of development of pleural fibrosis remain unclear. 3 Potts DE Levine DC Sahn SA Pleural fluid pH in parapneumonic effusions. Chest. 1976; 31: 70-328 Google Scholar The role of pleural inflammatory cells in the resolution of inflammation has not yet been elucidated. Since active inflammation is associated with the presence of neutrophils in the pleural fluid and resolution with the presence of mononuclear phagocytes, we hypothesized that pleural macrophages play a key role by inhibiting fibroblast proliferation. To evaluate our hypothesis we developed a model of mixed bacterial empyema in New Zealand white rabbits. Under light anesthesia induced by intravenous sodium pentobarbital (25 mg/kg), a catheter was inserted percutaneously between the spine and tip of the scapula into the right pleural space. 4 Sahn SA Antony VB Pathogenesis of pleural plaques: relationship of early cellular response and pathology. Am Rev Respir Dis. 1984; 87: 130-884 Google Scholar Escherichia coli, Peptostreptococcus sp, and Bacteroides fragilis, 1×10 8 Clark JG Kostal KM Macino BA Bleomycin induced pulmonary fibrosis in hamsters an alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphage and suppresses fibroblast proliferation and collagen production. J Clin Invest. 1983; 91: 72-2092 Google Scholar CFU each, were injected into the pleural space, creating an empyema. These strains were initially isolated from the blood of patients with sepsis and were selected, since mixed infections with Gram-negative facultative bacteria and anaerobes now preponderate in human empyemas. Moxalactam standard powder (lot no. S1113-0), with potency of 897 mg/kg, was supplied by the Lilly Research Laboratories and was stored in ampules at 4°C until used. The minimal inhibitory concentrations of moxalactam for the E coli, Peptostreptococcus sp, and B fragilis strains used were 0.1, 1.0, and 0.2 mg/ml, respectively. Moxalactam was administered in a dosage of 50 mkg/kg IM every 12 h in half of the animals. Thoracocentesis were done in all rabbits immediately before instillation of the mixed bacterial culture, 4 h following injection of bacteria, and every 24 h thereafter for the next 120 h. 5 Sahn SA Reller LB Taryle DA Antony VB Good Jr., JT The contribution of leukocytes and bacteria to the low pH of empyema fluid. Am Rev Respir Dis. 1983; 15: 128-811 Google Scholar