Pulmonary surfactant inhibits activation of human monocytes by recombinant interferon-gamma.
During an inflammatory reaction in the alveoli, the functional activities of monocytes, macrophages and granulocytes are regulated by a complex network of inflammatory mediators. The primary cytokine involved in 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 activation 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, and the production of H2O2 by rIFN-gamma-activated monocytes. Since our surfactant preparation stimulated the basal production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) by monocytes, the effect of Survanta, a surfactant extract, on the rIFN-gamma-induced production of these cytokines by monocytes was studied. The results revealed that Survanta caused 80-90% inhibition of the rIFN-gamma-induced production of TNF-alpha and IL-1 beta by these cells. Together, these results could mean that surfactant is involved in the protection of the alveolar epithelium against injury caused by reactive oxygen intermediates (ROI) and TNF-alpha, and in the down-regulation of the production of inflammatory mediators. In view of these considerations, surfactant therapy may not only improve lung compliance and gas exchange but may also be beneficial in reducing the inflammatory reaction in the lungs.
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
M F
MF
Geertsma
W L
WL
Teeuw
P H
PH
Nibbering
R
R
van Furth
D001688:Biological Products; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001688:Biological Products; D006681:HLA-D Antigens; D007375:Interleukin-1; D011663:Pulmonary Surfactants; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; C072197:beractant