Regulation of cytokine release by alveolar macrophages treated with interleukin-4, interleukin-10, or transforming

G Zissel1, J Schlaak, M Schlaak

  • 1Research Centre Borstel, Department of Clinical Medicine, Germany.

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.

Related Concept Videos

Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...