INTERLEUKIN-1 PRODUCTION IS DEFECTIVE IN ALVEOLAR MACROPHAGES FROM PATIENTS WITH LUNG-CANCER

Aim - To determine whether interleukin-1 (IL-1) production by pulmonary alveolar macrophages (PAM) is impaired in patients with lung cancer. Patients - Eleven untreated patients with bronchogenic carcinoma and ten control subjects, including seven without demonstrable pulmonary abnormality undergoing bronchoscopy for investigation of chronic cough or haemoptysis, and three normal volunteers. Interventions - Bronchoalveolar lavage (BAL) with subsequent measurement of IL-1. Measurements and main results - IL-1 was measured by a thymocyte proliferation assay in PAM supernatants after a four-hour incubation in the presence or absence of gamma interferon or endotoxin. Whereas IL-1 was found in the unstimulated supernatants from seven out of nine control subjects (1.25 +/- 0.5 units/10(6) PAM), it was present in the unstimulated supernatant of only one out of 11 cancer subjects (0.16 +/- 0.2 units/10(6) PAM) (p<0.05). Gamma interferon or endotoxin increased IL-1 in eight of nine control supernatants. Small amounts of IL-1 were measured in three of eight cancer supernatants after endotoxin, and in four of nine cancer supernatants after gamma interferon. Conclusions - IL-1 is generally not produced by unstimulated alveolar macrophages from lung cancer patients, whereas it is produced in small amounts by those from control subjects. However, macrophages from some cancer patients can be induced to produce IL-1 after activation with endotoxin or gamma interferon. The mechanism for the reduced IL-1 production by cancer macrophages is unclear, but this difference does not appear to reflect the presence of inhibitors.