Open AccessIn vivo boosting of lung natural killer and lymphokine‐activated killer cell activity by interleukin‐2: comparison of systemic, intrapleural and inhalation routes
Author(s) -
FLEXMAN J.P.,
MANNING L.S.,
ROBINSON B.W.S.
Publication year - 1990
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1990.tb05419.x
Subject(s) - immunology , lymphokine , natural killer cell , lymphokine activated killer cell , boosting (machine learning) , in vivo , medicine , interleukin 2 , inhalation , natural killer t cell , cytokine , biology , t cell , cytotoxic t cell , in vitro , immune system , interleukin 21 , anesthesia , biochemistry , microbiology and biotechnology , machine learning , computer science
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<0.05 versus controls for both). Surprisingly, inhaled IL‐2 suppressed both splenic and lung NK cell activity (84.8% and 78 ± 10% suppression, respectively, P<0.05). LAK cell activity was also enhanced in the lung by 1.8‐8‐fold in response to i.v., i.p. and intrapleural IL‐2, whereas inhaled IL‐2 was ineffective in generating LAK cell activity. These results suggest that the systemic and intrapleural administration of IL‐2 effectively boost pulmonary NK and LAK activity whereas inhalation of IL‐2 does not. Thus, in clinical situations where boosting of local lung NK or LAK cell activity is desired, these routes of IL‐2 administration may be effective.