PC-PS LIPOSOMES INDUCE A RECRUITMENT OF NEUTROPHILS AND THE RELEASE OF TNF-ALPHA IN THE LUNGS OF MICE SENSITIZED WITH SACCHAROPOLYSPORA-RECTIVIRGULA

The aim of this study was to verify the effect of nasally instilled li posomes (L) or dexamethasone-containing L (Ldexa) on normal or inflame d lung tissue. Three groups of mice were studied. Group I was given sa line instillations for 3 weeks prior to the instillation with liposome s. In groups II and III lung inflammation was induced by repeated inst illations of Saccharopolyspora rectivirgula before the instillation of liposomes (group II) or liposomes containing dexamethasone (group III ). Animals from all groups were killed at regular time intervals for u p to 48 h after the instillation of liposomes. The total cell count in bronchoalveolar lavage fluid did not differ si,snificantly between gr oups I and II. However, in group III it decreased rapidly from 6.2 to 2.8 x 10(5) cells mL(-1) within 2 h. Differential counts did not chang e in group I, but in group II a transient neutrophilia was observed 18 0 min after the instillation of liposomes. In group III, the instillat ion of dexamethasone-containing liposomes depleted all neutrophils and lymphocytes after 4 h. No TNF alpha was found in samples of lavage fl uid from any of the groups at time 0. In group I, liposomes induced th e production of 0.03 ng mL(-1) of TNF alpha in the 1 h sample only. In group II, TNF alpha peaked to 1 ng mL(-1) at 1 h and had decreased to 0.35 ng mL(-1) by 3 h. In group III, TNF alpha peaked at 1 h, but onl y reached a level of 0.1 ng mL(-1) It is concluded that liposomes caus e few acute inflammatory effects when instilled in normal lungs, altho ugh in the presence of an underlying inflammation these lipids can ind uce a further neutrophilic response and the release of TNF alpha. Howe ver, this response and the underlying inflammation are inhibited by th e incorporation of dexamethasone into the liposomes.