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 transplan t recipients, is a fibrotic process probably related to acute rejectio n (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesi s of pulmonary fibrotic diseases involves activation of alveolar macro phages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor nec rosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants ob tained 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 = 3,7 09 +/- 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 p attern 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 i n 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 I L-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.