MONITORING OF ALVEOLAR MACROPHAGE PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 IN LUNG-TRANSPLANT RECIPIENTS

Bronchiolitis obliterans (BO), a common complication in lung transplant recipients, is a fibrotic process probably related to acute rejection (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesis of pulmonary fibrotic diseases involves activation of alveolar macrophages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants obtained from 29 transplant recipients by immunoradiometric assay. Five groups were analyzed: AR (n = 21), CMVP(n = 12), BO(n = 15), bacterial pneumonia (BP)(n = 8), and control subjects (n = 70). Cytokines were also assayed 15 d (n = 15) and 30 d (n = 9) after AR and 30 d (n = 9) after CMVP. Cytokine secretion was elevated during AR (TNF-alpha = 3,709 +/- 1,409 pg/10(6) cells, IL-6 = 5,482 +/- 2,058 pg/10(6) cells, p < 0.005), and they returned to control values within 15 d. A similar pattern was observed during CMVP (TNF-alpha = 5,000 +/- 2,773 pg/10(6) cells, IL-6 = 12,280 +/- 3,939 pg/10(6) cells, p < 0.005), and values returned to control levels within 30 d. During BP, cytokine production values were higher than control values, but to a lesser extent than in AR and CMVP (TNF-alpha = 2,502 +/- 1,072, p < 0.05; IL-6 = 3,734 +/- 1,440, p < 0.005). In contrast, cytokine secretion during BO was not statistically different from that of control subjects. TNF-alpha and IL-6 secretions were strongly correlated (IL-6 = 1.38 TNF-alpha +/- 502, R(2) = 0.84, p < 0.0001). These findings show that AM are activated during CMVP and AR.