Acute non-immunological inflammation inhibits natural killer (NK) activity in the lungs and enhances metastatic development.

A non-immunological acute inflammatory reaction, induced in rats by intrapleural injection of calcium pyrophosphate microcrystals, decreased natural killer activity of lung intracapillary leucocytes (LICL), and, to a lesser extent, of spleen cells. NK activity was significantly depressed as early as 2 h after pleurisy induction, maximally suppressed at 72 h (when the inflammation had resolved) and returned to near-normal values by day 10. This decrease in NK activity was demonstrated using YAC-I lymphoma cells and syngeneic fibrohistiocytoma (P77) cells, as targets. The inhibition of NK activity of LICL was accompanied by an impaired destruction of P77 tumour cells injected i.v. 3 days after the onset of pleurisy. This was shown by an increase in the number of radiolabelled tumour cells surviving in the lungs at 24 h and of tumour nodules developed in lung parenchyma at 3 weeks. Suppression of NK activity was not due to a decrease in the proportion of large granular lymphocytes (LGL) in the LICL population. Suppressor macrophages may be involved, at least in part, since a partial restoration of LICL cytotoxicity was obtained after depletion of plastic-adherent cells. The effect of inflammation was reproduced in normal rats by injecting inflammatory serum or PGE2, suggesting a possible role of circulating mediators.