Regulation of cytokine release by alveolar macrophages treated with interleukin-4, interleukin-10, or transforming growth factor beta.
We evaluate the influence of IL-4, IL-10 and TGF-beta upon the release of IL-1 alpha, tumor necrosis factor-alpha (TNF-alpha), and IL-6 by lipopolisaccharide (LPS, 1 microgram/ml) stimulated alveolar macrophages (AM). IL-4 reduced TNF-alpha release, in a dose dependent manner, to 62% and IL-1 alpha release to 42% of LPS-stimulated AM without IL-4. IL-6 release was also suppressed (61%), however, with a biphasic dose response curve. IL-10 suppressed LPS induced release of IL-alpha and TNF-alpha to approximately 50% of control without affecting IL-6 release. When used at high concentrations, TGF-beta achieved moderate reductions of TNF-alpha and IL-1 alpha release. Low concentrations of LPS (0.1 microgram/ml), allowed a dose-dependent TGF-beta-induced suppression of TNF-alpha-release to approximately 80% of control. The combinations of IL-4 and IL-10 was more effective in suppressing IL-6 release, although the suppression was only weak. Other combinations of cytokines revealed no synergistic inhibitory activities. Our data demonstrate that IL-1 alpha and TNF-alpha release by AMs is down regulated by IL-4, IL-10, and TGF-beta. IL-6 release, however, can only be suppressed to some extent by a combination of IL-4 and IL-10.
Zissel
G
G
Research Centre Borstel, Department of Clinical Medicine, Germany.
Schlaak
J
J
Schlaak
M
M
Müller-Quernheim
J
J
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4