Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis.
An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of the active group, i.e., 2,385 +/- 735 pg/ml/10(8) cells/24 h and 7/12 (IL-1+/total), respectively. Autologous PBMNC were quiescent, releasing only baseline levels of any monokine. AM were not activated in the inactive group, releasing 500 +/- 212 pg/ml/10(6) cells/24 h TNF alpha, whereas 1/5 were IL-1-positive (p less than 0.05 in both comparisons), which is within the range of the control group. Kinetic experiments revealed that the TNF alpha gene of AM is activated in vivo, resulting in TNF alpha mRNA-positive, TNF alpha-releasing cells that, cultured in vitro, regulate the TNF alpha gene transcription down and cease to release TNF alpha. Interestingly, there is no stringent correlation between the spontaneous release of TNF alpha by AM and signs of T-cell activation as soluble interleukin-2 (IL-2) receptor serum concentration, release of IL-2, and expression of IL-2 receptor by alveolar T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Müller-Quernheim
J
J
IIIrd Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany.
Pfeifer
S
S
Männel
D
D
Strausz
J
J
Ferlinz
R
R
D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012507:Sarcoidosis / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha