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 chemical-induced tumors. However, its effects on lung immunity after inhalation, a common route for human exposure in urban areas, has not been determined. These studies examine intratracheal B(a)P instillation on lung natural killer (NK) cell activity, alveolar macrophage (AM) functions, and susceptibility to tumor cell challenge in Fischer 344 (F-344) rats. Adult female F-344 rats were given a single intratracheal instillation of 0, 10, 20, or 40 mg B(a)P/kg body weight as a suspension, and 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 significant suppression of H2O2 and nitric oxide (NO) release from alveolar macrophages of treated animals as well as NK cell activity from the lung digest. A marked suppression of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL-1) secretion in LPS- and/or cytokine-activated alveolar macrophages occurred. The suppressive effects were generally more 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 allowed for the increased growth of MADB106 metastatic tumor cells in the lung. These tumor cells were shown to be highly sensitive to lysis by immune-mediators, including TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)