Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from healthy donors, and their abilities to produce extracellular and cell-associated interleukin 1 (IL-1) in response to various activation stimuli were compared with those of autologous blood monocytes. The production of IL-1 alpha and IL-1 beta by monocytes and AM was examined by thymocyte co-stimulation assay and enzyme immunoassays (EIA). Results showed that when activated with lipopolysaccharide (LPS) or desmethyl muramyl dipeptide (norMDP), AM released much less extracellular IL-1 beta than did blood monocytes. In contrast, these activated AM produced more cell-associated IL-1 than did blood monocytes. When the IL-1 activity was examined by the thymocyte assay, the extracellular and cell-associated IL-1 produced by the two cell types were largely IL-1 beta and IL-1 alpha, respectively, as shown by antibody neutralization. The cell-associated IL-1 activity of AM induced by the synergistic actions of suboptimal concentrations of recombinant interferon-gamma (rIFN-gamma) and norMDP was also higher than that of autologous blood monocytes. Consistent with these findings on AM, macrophages generated in vitro by maturation of blood monocytes produced higher levels of cell-associated IL-1 activity than did freshly isolated monocytes. These observations suggest that AM may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell-associated IL-1 alpha.

The effect of interleukin 4 (IL‐4) on expression of antitumor activity of blood monocytes purified by counter‐flow centrifugal elutriation from healthy donors was examined. The blood monocytes were incubated for 24 h in medium with lipopolysaccharide, interferon γ (IFN‐γ) or desmethyl muramyl dipeptide (norMDP) or with IFN‐γ and norMDP in the presence of IL‐4, and then their tumoricidal activity was assayed by measuring 125IUdR release from human melanoma (A375) cells. Irrespective of activation stimulus, addition of IL‐4 to cultures of monocytes and activators resulted in dose‐dependent suppression of the tumoricidal activity of monocytes against parent A375 melanoma cells and the variant cells, A375‐R resistant to IL‐1 and tumor necrosis factor α. IL‐4 suppressed the early induction phase of monocyte activation. Rabbit anti‐IL‐4 antisera completely blocked the IL‐4‐mediated suppression of monocyte activation to the tumoricidal state. These findings suggest that IL‐4 is important in vivo in down‐regulation of anti‐tumor expression of monocytes.

The abilities of human alveolar macrophages (AM) obtained from healthy donors and patients with lung cancer to produce tumor necrosis factor (TNF) were compared with those of their blood monocytes after activation with lipopolysaccharide (LPS). TNF activity was assayed by measuring cytotoxicity against actinomycin D‐treated L929 cells and TNF was determined quantitatively by sandwich enzyme‐linked immnnosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF‐α. Unstimulated AM from healthy donors released variable amounts of TNF spontaneously, whereas blood monocytes did not. When treated with LPS for 24 h, AM and monocytes produced TNF dose‐dependently, but TNF production by AM was significantly more than that by blood monocytes. This TNF activity was inhibited completely by monoclonal anti‐TNF‐α antibody. Macrophages generated by in vitro maturation of monocytes induced by granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) produced more TNF than freshly isolated monocytes. No difference was found in the abilities of AM from healthy donors and patients with lung cancer to produce TNF after activation stimuli. These observations suggest that human AM may be important in in vivo antitumor defense of the lung through TNF‐α production.

A 35-year-old man was hospitalized with complaints of retrosternal pain and high fever. A chest radiograph showed a large round mass in the mediastinum. Of the several tumor markers in the serum tested, only CA 19-9 was elevated. Thoracotomy revealed a cystic mass with purulent hemorrhagic materials. Histologically the cyst was lined by bronchial epithelium with no evidence of malignancy. The high level of CA 19-9 in the cystic fluid, and positive immunohistochemical staining of the bronchial glands in the cyst wall for CA 19-9 indicated that the elevated serum level of CA 19-9 originated from the bronchogenic cyst after its infection.

The effects of lung cancer on the abilities of blood monocytes to produce interleukin-1 and to mediate antitumor activity were examined. The functional integrity of blood monocytes was determined by their capacity to respond in vitro to a variety of activating agents and become tumoricidal, as assessed by a radioactive release assay and ability to produce interleukin-1 in vitro. The results show that the presence of lung cancer significantly increased the number of harvested blood monocytes and that the spontaneous tumoricidal activity of these monocytes was slightly high as compared to monocytes obtained from healthy donors. The production of interleukin-1 by monocytes of healthy donors and lung cancer patients was similar. Blood monocytes obtained from lung cancer patients were less cytotoxic against allogeneic A375 melanoma cells as compared with those of healthy donors subsequent to incubation with a soluble muramyl dipeptide analog or lipopolysaccharide, but were as tumoricidal as those from healthy donors when activated with lipophilic muramyl tripeptide (MTP-PE) entrapped in multilamellar liposomes. The finding that monocytes of patients with lung cancer can respond to MTP-PE encapsulated in liposomes, recommends the use of these liposomes in therapy of human lung cancer.