INHIBITION OF LUNG IMMUNITY AFTER INTRATRACHEAL INSTILLATION OF BENZO(A)PYRENE

Benzo(a)pyrene (B(a)P) has been shown to suppress systemic immunity in experimental animals, which may contribute to the growth of the chemi cal-induced tumors. However, its effects on lung immunity after inhala tion, a common route for human exposure in urban areas, has not been d etermined. These studies examine intratracheal B(a)P instillation on l ung natural killer (NK) cell activity, alveolar macrophage (AM) functi ons, and susceptibility to tumor cell challenge in Fischer 344 (F-344) rats. Adult female F-344 rats were given a single intratracheal insti llation of 0, 10, 20, or 40 mg B(a)P/kg body weight as a suspension, a nd lung NK cell activity and AM functions were examined 7, 21, or 100 d later. Although exposure to B(a)P did not alter cell recovery after lavage, histologic changes were observed as evidenced by granulomatous inflammation and squamous metaplasia. There was a slight but signific ant suppression of H2O2 and nitric oxide (NO) release from alveolar ma crophages of treated animals as well as NK cell activity from the lung digest. A marked suppression of tumor necrosis factor alpha (TNF alph a) and interleukin (IL-1) secretion in LPS-and/or cytokine-activated a lveolar macrophages occurred. The suppressive effects were generally m ore severe on Day 7 after exposure than on Days 21 or 100, although IL -1 remained depressed through Day 100 after exposure. B(a)P exposure a llowed for the increased growth of MADB106 metastatic tumor cells in t he lung. These tumor cells were shown to be highly sensitive to lysis by immune-mediators, including TNF alpha. Taken together, these result s indicated that NK cell activity and particularly secretory products produced by AM are sensitive targets for instilled B(a)P, and altered lung immunity may play a role in allowing for the growth of lung tumor s.