PULMONARY SURFACTANT INHIBITS ACTIVATION OF HUMAN MONOCYTES BY RECOMBINANT INTERFERON-GAMMA

During an inflammatory reaction in the alveoli, the functional activit ies of monocytes, macrophages and granulocytes are regulated by a comp lex network of inflammatory mediators. The primary cytokine involved i n activation of these phagocytes is interferon-gamma (IFN-gamma). The possible influence of local factors, such as pulmonary surfactant, on the activation process has not been studied until now. The aim of the present study was to investigate the effects of surfactant on the acti vation of monocytes by recombinant (r)IFN-gamma. The results revealed that human surfactant significantly inhibited both the increase in the expression of the high-affinity receptor for IgG, i.e. Fc gamma RI, a nd the production of H2O2 by rIFN-gamma-activated monocytes. Since our surfactant preparation stimulated the basal production of tumour necr osis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) by mo nocytes, the effect of Survanta(R), a surfactant extract, on the rIFN- gamma-induced production of these cytokines by monocytes was studied. The results revealed that Survanta(R) caused 80-90% inhibition of the rIFN-gamma-induced production of TNF-alpha and IL-1 beta by these cell s. Together, these results could mean that surfactant is involved in t he protection of the alveolar epithelium against injury caused by reac tive oxygen intermediates (ROI) and TNF-alpha, and in the down-regulat ion of the production of inflammatory mediators. In view of these cons iderations, surfactant therapy may not only improve lung compliance an d gas exchange but may also be beneficial in reducing the inflammatory reaction in the lungs.