Influence of royal jell and bee pollen on cytokines production, PART III

Ahmed Hegazi
Professor of Microbiology and Immunology
National Research Center, Dokki, Giza, Egypt
Member of Apitherapy Commission, APIMONDIA
E mail: ahmedgaffer@mailer.eun.eg and ahmedhegazi128@gmail.com

Medical scientist discovered that all living creatures have their own ways to protect their new generation. Human, Bovine and avian species delivers their antibody to protect their embryos from viral infection (Korhonen & Syvaeoja, 1995 and. Chan & Kummer, 1995). Bee's royal jelly and honey contains immunoglobulin to protect bee's larva form bacterial and viral infections. Hymenoptera (Apis mellifera) venom contains venom specific immunoglobins and cytokines provide effective immunotherapy for viral and bacterial infections.

The action of cytokines may be autocrine, paracrine, and endocrine. Cytokines are critical to the development and functioning of both the innate and adaptive immune responses. They are often secreted by immune cells that have encountered a pathogen, thereby activating and recruiting further immune cells to increase the system's response to the pathogen.

A classification of the function of the cytokine that proves more useful in clinical and experimental practice which divides immunological cytokines into those that enhance cytokine responses, type 1 (IFN-γ, TGF-β, etc.), and type 2 (IL-4, IL-10, IL-13, etc.), which favor antibody responses.

Cytokines have been classed as lymphokines, interleukins and chemokines, based on their presumed function, cell of secretion, or target of action. Effect of each cytokine has a matching cell-surface receptor. Subsequent cascades of intracellular signalling then alter cell functions

Royal Jelly

Kohno et al., (2004) examined the anti-inflammatory actions of royal jelly (RJ) at a cytokine level. When supernatants of RJ suspensions were added to a culture of mouse peritoneal macrophages stimulated with lipopolysaccharide and IFN-gamma, the production of proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-1, was efficiently inhibited in a dose-dependent manner without having cytotoxic effects on macrophages. This suggests that RJ contains factor(s) responsible for the suppression of proinflammatory cytokine secretion. We named the factor for honeybees RJ-derived anti-inflammatory factor (HBRJ-AIF), Royal jelly treatment in lymphocytes from patients with Graves' disease shifted the Th1/Th2 cytokine ratio to the side of Th1 cytokine. Therefore, Royal jelly using the treatment and establishing a remission of Graves' disease may be effective as an antithyroid drug treatment (Erem et al., 2006).

Pollen

At the mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E(1)-phytoprostanes (PPE(1)) were identified to modulate dendritic cell (DC) function: PPE(1) inhibit the DC's capacity to produce IL-12 and enhance DC mediated T(H)2 polarization of naive T cells. The mechanism(s) by which PPE(1) act on DC remained elusive. Gilles et al., (2009) analyzed role in PPE(1)-mediated regulation of DC function. Aqueous birch pollen extracts induced a marked cAMP response in DC that could be blocked partially by EP2 and EP4 antagonists. In contrast, PPE(1) hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE(1) inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-gamma. Finally, PPE(1) efficiently blocked NF-kappaB signaling in DCs by inhibiting IkappaB-alpha degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE(1) modulate DC function via PPAR-gamma dependent pathways that lead to inhibition of NFkappaB activation and result in reduced DC IL-12 production and consecutive T(H)2 polarization. Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive. Lewis et al., (2009) clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis. They found a signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells. They concluded that IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-gamma response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease. Miyoshi-Higashino et al., (2009) suggested that IgE+ basophils in the peripheral blood, and IgE+ B cells in the spleen, might be IL-4-dependently induced as an indicator of sensitization with allergen, and a precursor of cells secreting allergen-specific IgE antibody respectively.

References:
Chan,E.L.,Kummer,A.(1995). Survey of Immunoglobulin G Content and Antibodies Specificity in Cow's Milk from British Columbia.
Food and Agricultural Immunology, 6,443-451.
Erem C, Deger O, Ovali E, Barlak Y. (2006)The effects of royal jelly on autoimmunity in Graves' disease. Endocrine. 30(2):175-83.
Gilles S, Mariani V, Bryce M, Mueller MJ, Ring J, Jakob T, Pastore S, Behrendt H,
Traidl-Hoffmann C.(2009 ) Pollen-derived E1-phytoprostanes signal via PPAR-gamma and NF-kappaB-dependent mechanisms. J Immunol. 1;182(11):6653-8. Kohno K, Okamoto I, Sano O, Arai N, Iwaki K, Ikeda M, Kurimoto M. (2004) Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Biosci Biotechnol Biochem. 68(1):138-45.
Korhonen, H., Syvaeoja, E.L.(1995) Bacterial effect of Bovine Normal and Immune Serum, Colostrum and milk against Helicobacter Pylori. Journal of Applied Bacteriology, 78,655-662.
Lewis CC, Aronow B, Hutton J, Santeliz J, Dienger K, Herman N, Finkelman FD, Wills-Karp M.( 2009) Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung. J Allergy Clin Immunol. 123(4):795-804.
Miyoshi-Higashino M, Hirano M, Ogita-Nakanishi H, Yamamoto-Kimoto Y, Sakurai K, Tashiro-Yamaji J, Nomi H,Takahashi T, Miura-Takeda S, Takenaka H, Kubota T, Yoshida R.( 2009) IL-4-dependent induction of IgE basophils in peripheral blood and IgE B cells in spleen as respective indicators of allergen sensitization and a precursor of cells secreting allergen-specific IgE antibody. Microbiol Immunol. 53(1):30-40.