Monday, September 28, 2009

Propolis in Correlation to Cytokines - Part II

Apitherapy Review, Fall 2009

By Ahmed Hegazi
Professor of Microbiology and Immunology
National Research Center , Dokki, Giza , Egypt
Member of Apitherapy Commission, APIMONDIA
E-mail: and

Propolis, the resinous product collected by honey bees from plants, is used as folk medicine since ancient time. During the last ten years, immunoregulatory and anti-inflammatory properties of propolis have been published.

Cytokines (Greek cyto-, cell; and -kinos, movement) are a category of signaling molecules that are used extensively in cellular communication. They are proteins, peptides, or glycoproteins. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin. (Gilman et al., 2001). Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis.

Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes)…

The detailed mechanisms of actions of propolis and its components on immune cells, however, are still unknown. Inflammatory cytokines and oxidative stress have a central role in the pathogenesis of acute pancreatitis. Propolis has anti-inflammatory and anti-oxidant effects. Büyükberber et al., (2009) investigated the therapeutic role of ethanolic extract of propolis on a cerulein-induced acute pancreatitis model in rats. In the acute pancreatitis group, serum amylase and lipase levels were found to be elevated and the histopathological evaluation of the tissue revealed massive edema and inflammation with less fatty necrosis when compared to the sham and control groups. In the ethanolic extract of propolis group, in particular, tissue edema was improved markedly (p=0.001). Tissue inflammation and fatty necrosis were decreased with ethanolic extract of propolis treatment.

In most of the diseases which are considered to benefit from propolis, cellular immune reaction is activated, neopterin levels in body fluids are increased and enhanced tryptophan degradation is observed. Girgin et al., (2009) studied, the immunomodulatory effects of six Turkish propolis samples were evaluated by using the in vitro model of peripheral blood mononuclear cells (PBMC). Concentrations of neopterin, tryptophan, kynurenine and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined. In PBMC treated with mitogen phytohaemagglutinin, neopterin production and tryptophan degradation by enzyme indoleamine 2,3-dioxygenase (IDO) as well as release of cytokines was significantly enhanced and upon treatment with propolis extracts all these effects were dose-dependently suppressed.

CAPE is a biologically active component of propolis, a resinous material obtained from bee hives. The effect of CAPE on lipopolysaccharide (LPS)-induced inflammatory reactions is not known. Song et al., (2008) evaluated the anti-inflammatory effect of CAPE on cultured human middle ear epithelial cells (HMEECs). They suggested that the anti-inflammatory effect of caffeic acid phenethyl ester ( CAPE ) is due to its inhibition of tumor necrosis factor (TNF)-alpha expression and interleukin (IL)-8 production. The anti-inflammatory effect of CAPE is possibly through the inhibition of nuclear factor (NF)-kappaB via the suppression of inhibitor-kappaB-alpha (IkappaB-alpha) degradation…

The immune system has a variety of regulatory/suppressive processes, which are decisive for the development of a healthy or an allergic immune response to allergens. NK1 and NK2 subsets have been demonstrated to display counterregulatory and provocative roles in immune responses, similar to Th1 and Th2 cells. T regulatory cells suppressing both Th1 and Th2 responses have been the focus of intensive research during the last decade. Deniz et al., (2008) investigated the regulatory NK cells in humans, by characterization of NK cell subsets according to their IL-10 secretion property. Freshly purified IL-10-secreting NK cells expressed up to 40-fold increase in IL-10. The effect of IL-10+ NK cells on Ag-specific T cell proliferation has been examined in bee venom major allergen, phospholipase A2- and purified protein derivative of Mycobecterium bovis-induced T cell proliferation. IL-10+ NK cells significantly suppressed both allergen/Ag-induced T cell proliferation and secretion of IL-13 and IFN-gamma, particularly due to secreted IL-10 as demonstrated by blocking of the IL-10 receptor. These results demonstrate that a distinct small fraction of NK cells display regulatory functions in humans.

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