In vivo boosting of lung natural killer and lymphokine‐activated killer cell activity by interleukin‐2: comparison of systemic, intrapleural and inhalation routes

SUMMARY Natural killer (NK) cells are thought to play a role in host defence against malignancy and infection, in immunoregulation and as precursor cells in a generation of lymphokine‐activated killer (LAK) cells which can lyse NK‐resistant tumour cells. As the lung is a major site for malignancy and infection and as there are large numbers of lymphoid cells including NK cells in the interstitial compartment of the lung, we evaluated the capacity of interleukin‐2 (1L‐2), a lymphokine capable of augmenting NK activity in vitro, to augment lung NK cell activity in vivo, usingdifferent routes ofIL‐2 administration. We compared both systemic (i.v. and i.p.) and local (intrapleural and inhalation) routes of IL‐2 administration (50000 UJdaily for 5 days) using CBA mice, assessing NK and LAK cell activity in the spleen (systemic) and in the lung. The target cells used for these studies were the YAC‐1 (NK‐sensitive) and P815, NO36 and HA56 (NK‐resistant, LAK‐sensitive) cell lines. Splenic NK activity was increased by 1.4‐1 1.9‐fold for i.v./i.p., respectively, compared with controls with both systemic routes of administration, and lung NK activity was increased 3‐2‐fold and 3‐8‐fold (i.v./i.p, respectively, P < 0.05), to levels which were comparable to systemic (splenic) NK activity following the same therapy. Intrapleural IL‐2 administration similarly enhanced lung NK activity (3‐3‐fold) and splenic NK activity (1.3‐fold; P