Cytokine or immunocytokine is a generic name used to describe a diverse group of soluble proteins and peptides which act as humoral regulators at nano- to- picomolar concentrations
Cytokine or immunocytokine is a generic name used to describe a diverse group of soluble proteins and peptides which act as humoral regulators at nano- to- picomolar concentrations
Cytokine or immunocytokine is a generic name used to describe a diverse group of soluble proteins and peptides which act as humoral regulators at nano- to- picomolar concentrations
Cytokines modulate the functional activities of individual cells and tissues both under normal and pathologic conditions
“Cytokines” are soluble protein secreted by the cells of innate and adaptive immunity and therefore mediate many of the functions of these cells
“Cytokines” are soluble protein secreted by the cells of innate and adaptive immunity and therefore mediate many of the functions of these cells
A subfamily of cytokines primarily functions in directing migration of cells, these are called “chemotactic cytokines” or “chemokines”
1.Most cytokines are low molecular weight polypeptides or glycoprotein(8~80 KD), and most of them are monomer.
1.Most cytokines are low molecular weight polypeptides or glycoprotein(8~80 KD), and most of them are monomer.
2. Natural cytokines are secreted by activated cells
2. Natural cytokines are secreted by activated cells
Such as activated immune cells,
matrix cells
some tumor cells.
Ag,
SAg,
mitogen
IL-3,GM-CSF,TNF-
Interleukins - produced exclusively by leukocytes
Interleukins - produced exclusively by leukocytes
Lymphokines - produced by lymphocytes
Monokines - produced exclusively by monocytes
Interferons - involved in antiviral responses
Colony Stimulating Factors - support the growth of cells in semisolid medias
Chemokines - promote chemotaxis.
Low molecular weight proteins, <30kD
Low molecular weight proteins, <30kD
High affinity for receptors
Active in picomole amounts
Innate immune response
Innate immune response
IL 1-(Macrophage)-fever, capillary effects
IL 6-(Macrophage)-adaptive immunity via B cells
IL 12(Macrophage)-adaptive immunity via T helper cells
IFN gamma-(T cells, NK cells)-Macrophage activation
The biological activities of cytokines can be measured by a variety of bioassays which may employ factor-dependent cell lines, or antibodies (ELISA)
The biological activities of cytokines can be measured by a variety of bioassays which may employ factor-dependent cell lines, or antibodies (ELISA)
RT-PCR quantitation of cytokines detects the presence of mRNA encoding specific cytokines
“Apitherapy” is, simply said, the use of bee products to prevent, heal or recover somebody from one or more diseases/conditions.
“Apitherapy” is, simply said, the use of bee products to prevent, heal or recover somebody from one or more diseases/conditions.
The origin of this word is Api" comes from the bee's latin name: Apis mellifica
"therapy" comes from the Greek word "therapeuein" which means a method to treat the human beings or animals against different diseases.
However, we understand today apitherapy in a much larger sense…
However, we understand today apitherapy in a much larger sense…
Apitherapy is not just a simple, therapeutically method; it is already a different type of medicine.
We can even call it "APIMEDICINE".
Usually people think of bees for honey
Usually people think of bees for honey
As pollinators—most valuable.
As pollinators—most valuable.
Honey bees produce honey, wax, propolis, and royal jelly.
Honey bees produce honey, wax, propolis, and royal jelly.
Bee venom use for bee sting therapy (Apitherapy).
Bee venom,
Bee venom,
Bee pollen,
Honey,
Royal jelly,
Propolis
are products from bees that are generally considered to have medicinal effects (Hegazi, 2009 a,b and Hegazi, 2010).
Bee products honey,
Bee products honey,
royal jelly (RJ)
bee pollen
belong to the extraordinaire components of human nutrition and are used in pharmaceutical and cosmetic industry.
These products contain physiologically active substances from floral origin of honey bee and plants origin (Aronne et al, 2014).
At different levels, in the human innate response, these compounds suppress
At different levels, in the human innate response, these compounds suppress
DNA synthesis,
decrease proinflammatory cytokine synthesis (IL-2, IL-12 and IL-4),
inactivate both the classical and alternative complement pathway,
decrease superoxide anion production in rabbit neutrophils.
propolis and honey induce the increase of antibody production by plasma cells,
propolis and honey induce the increase of antibody production by plasma cells,
enhance the secretion of TGF-β after the activation of T regulatory cells,
inhibit Con A-stimulated cell proliferation in mice ( Cova, 2013).
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 Mycobacterium bovis-induced T cell proliferation.
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 Mycobacterium 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.
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.
Honey has been used since ancient times as a remedy in wound care and antimicrobial activity (Hegazi et al., 2015)
Honey has been used since ancient times as a remedy in wound care and antimicrobial activity (Hegazi et al., 2015)
Certain inflammatory cytokines, particularly IL-1b and TNF-a, can also induce the production of the keratinocyte growth factor which can indirectly promote re-epithelialization (Kristensen et al., 1993 and Brauchle et al. 1994).
Keratinocytes express relatively high amounts of matrix metalloproteinase-9 (MMP-9), and this production can be additionally up-regulated by TGF-b, TNF-a or IL-1b (Salo et al. 1994).
Keratinocytes express relatively high amounts of matrix metalloproteinase-9 (MMP-9), and this production can be additionally up-regulated by TGF-b, TNF-a or IL-1b (Salo et al. 1994).
Keratinocytes, which are known to be involved in wound healing, are responsible for elevated production of mediators including cytokines (TNF-a, IL-1b and TGF-b) and matrix metalloproteinase-9 (MMP-9) after incubation with honey (Majtan et al. 2010).
Keratinocytes, which are known to be involved in wound healing, are responsible for elevated production of mediators including cytokines (TNF-a, IL-1b and TGF-b) and matrix metalloproteinase-9 (MMP-9) after incubation with honey (Majtan et al. 2010).
The roles of tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and interleukin-6 (IL-6) are also important in the inflammatory response.
The roles of tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and interleukin-6 (IL-6) are also important in the inflammatory response.
Important role for natural honey in modulating immune response.
Important role for natural honey in modulating immune response.
Tonks et al., (2003) investigated the effects of honey on the activation state of immunocompetent cells, using the monocytic cell line, MonoMac-6 (MM6), as a model the release of important inflammatory cytokines from MM6 cells
They assayed the tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and IL-6.
They assayed the tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and IL-6.
All honeys significantly increased the TNF-α, IL-1β and IL-6 release from MM6 cells (and human monocytes) when compared with untreated and artificial-honey-treated cells (P<0.001).
The production of pro-inflammatory cytokines IL-1β and TNF-α by human monocytic cell line in the presence of honey proteins was analyzed.
The production of pro-inflammatory cytokines IL-1β and TNF-α by human monocytic cell line in the presence of honey proteins was analyzed.
Honey proteins did not affect the production of IL-1β; however, TNF-α production was significantly suppressed (Mesaik et al., 2015).
Tonks et al. (2003) suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages.
Tonks et al. (2003) suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages.
The findings show that natural honeys can induce IL-6, IL-1b, and TNF-a release.
Honey has been shown to have mitogenic activity on human B and T lymphocytes.
Honey has been shown to have mitogenic activity on human B and T lymphocytes.
The proliferation of peripheral blood B-lymphocytes and T-lymphocytes in cell culture is stimulated by honey at concentrations as low as 0.1%; and phagocytes are activated by honey at concentrations as low as 0.1% (Abuharfeil et al., 1999).
Honey (at a concentration of 1%) also stimulates monocytes in cell culture to release
Honey (at a concentration of 1%) also stimulates monocytes in cell culture to release
cytokines,
tumor necrosis factor (TNF)-alpha,
interleukin (IL)-1
IL-6,
which activate the immune response to infection (Tonks et al., 2001)
Proteins present in honey will be highly glycosylated because of high sugar content.
Proteins present in honey will be highly glycosylated because of high sugar content.
Glycosylated proteins have been shown to activate a number of cell types including monocyte cells (Brownlee, 1995).
The protein fraction of RJ contains many valuable components and biologically active substances.
The protein fraction of RJ contains many valuable components and biologically active substances.
Besides the MRJPs, low amounts of several minor proteins including antibiotics peptides (Fujiwara et al., 1990; Bilikova et al., 2001; Bilikova et al., 2002) are present in RJ.
Kohno et al., (2004) examined the anti-inflammatory actions of royal jelly (RJ) at a cytokine level.
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.
This suggests that RJ contains factor(s) responsible for the suppression of proinflammatory cytokine secretion.
They named the factor for honeybee’s 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.
At the mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators.
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.
PPE(1) inhibit the DC's capacity to produce IL-12 and enhance DC mediated T(H)2 polarization of naive T cells.
pollen-derived PPE(1) modulate DC function which
pollen-derived PPE(1) modulate DC function which
lead to inhibition of NF kappa B 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.
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 hyper responsiveness and goblet cell hyperplasia.
Essentially the “glue” in bee hives.
Essentially the “glue” in bee hives.
Made of plant resin.
Preserves warmth in hive and keeps out microbes.
Has various antimicrobial properties.
Used for healing and part of “apitherapy”.
Interesting uses including violin varnish.
Used since the Ancient Egyptian, Greeks and Romans.
Caffeic acid phenethyl ether or CAPE.
Caffeic acid phenethyl ether or CAPE.
Phenolics
Terpenes
Hydrocarbons
Acids
Flavonoids
Stimulates antibody production.
Stimulates antibody production.
Inhibits viral entry into CD4 lymphocytes, especially against HIV-1.
Increases effectiveness of antiviral drugs such as the reverse transcriptase inhibitor, zidovudine.
Treats opportunistic infections that plague AIDS patients.
Treats opportunistic infections that plague AIDS patients.
Decreases lymphocyte proliferation when exposed to mitogens such as ConA.
Increases production of IFN-γ and activates macrophages.
Inhibits Nuclear Transcription Factor Kappa B or NF-κB, which drives T-cell proliferation and effector functions.
Inhibits Nuclear Transcription Factor Kappa B or NF-κB, which drives T-cell proliferation and effector functions.
Anti-inflammatory activity.
Treats arthritis and inflammatory bowel disease.
Inhibits IL-2 which also drives T-cell proliferation.
Propolis was shown to increase antibody production in rats immunized with bovine serum albumin.
Propolis was shown to increase antibody production in rats immunized with bovine serum albumin.
Acted as adjuvant.
Enhanced the activity of macrophages.
CAPE inhibited NF-κB binding to macrophages and decreased cytokine production.
CAPE inhibited NF-κB binding to macrophages and decreased cytokine production.
Tumor necrosis factor alpha, TNF-α, which stimulates macrophages to kill tumor cells was used to see if NF- κB would bind.
Anti-inflammatory activity.
Macrophages underwent apoptosis in patients with IBD leading to healing of the injuries to the colon.
CAPE inhibited IL-2 leading to anti-inflammatory activity.
CAPE inhibited IL-2 leading to anti-inflammatory activity.
T-cell proliferation was inhibited in samples with Con-A, a mitogen, added.
Viral entry of HIV-1 was inhibited in CD4 lymphocytes.
Viral entry of HIV-1 was inhibited in CD4 lymphocytes.
Effectiveness of the reverse transcriptase inhibitor, zidovudine, was increased.
Virus was kept from proliferating.
Propolis treats opportunistic fungal infections such as thrush and leukoplakia.
Propolis treats opportunistic fungal infections such as thrush and leukoplakia.
Kept infections from coming back and alleviated symptoms.
Increased the immune response.
Propolis increased IFN-γ production leading to the antigen being presented on cells and the immune response starting to clear it faster.
Propolis increased IFN-γ production leading to the antigen being presented on cells and the immune response starting to clear it faster.
Mitogen infected cells did not show proliferation that would normally happen.
Kept mitogen from working.
Propolis is an effective anti-inflammatory agent.
Propolis is an effective anti-inflammatory agent.
Can be used to help AIDS patients.
Controls inflammatory diseases.
Increases effectiveness of immune system.
Mechanisms are not known yet.
Ancient cure for today’s ailments.
Propolis, the resinous product collected by honey bees from plants, is used as folk medicine since ancient time.
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.
Inflammatory cytokines and oxidative stress have a central role in the pathogenesis of acute pancreatitis.
Propolis has anti-inflammatory and anti-oxidant effects.
Song et al., (2008) found 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.
Song et al., (2008) found 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)-kappa B via the suppression of inhibitor-kappa B-alpha (IkappaB-alpha) degradation
The anti-inflammatory effect of CAPE is possibly through the inhibition of nuclear factor (NF)-kappa B via the suppression of inhibitor-kappa B-alpha (IkappaB-alpha) degradation
Choi and Choi (2008) reported that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-kappa B inhibition by two distinct molecular mechanisms in a cell-specific manner:
Choi and Choi (2008) reported that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-kappa B inhibition by two distinct molecular mechanisms in a cell-specific manner:
CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in monocytic cells, while activation of upstream IkappaB kinase was suppressed by CAPE pre-treatment in astroglial cells
CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in monocytic cells, while activation of upstream IkappaB kinase was suppressed by CAPE pre-treatment in astroglial cells
and (ii) CAPE paradoxically activates the c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro-apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand-8.
Sy et al., (2006) found that the higher dose of propolis extracts decreases the level of IL- 5 in BALF.
Sy et al., (2006) found that the higher dose of propolis extracts decreases the level of IL- 5 in BALF.
The splenocytes from mice administered with propolis extracts (low- and high-dose groups) exhibit a strong inhibition of IL-10 secretion and up-regulation of IFN-gamma secretion in splenocytes stimulated with concanavalin A (ConA).
propolis stimulated splenocytes Cytokine (IFN-gamma, IL-6, and IL-10) secretion
propolis stimulated splenocytes Cytokine (IFN-gamma, IL-6, and IL-10) secretion
These results suggest that propolis extracts may be a potential novel therapeutic agent for asthma.
CAPE suppressed H. pylori-induced cell proliferation and production of the cytokines TNF-alpha and IL- 8.
CAPE suppressed H. pylori-induced cell proliferation and production of the cytokines TNF-alpha and IL- 8.
In addition, CAPE blocked H. pylori-induced COX-2 expression.
The inhibition of such transcription by CAPE could result in suppression of many genes during H. pylori-induced inflammation (Abdel-Latif et al., 2005)
Márquez et al., (2004) found that CAPE specifically inhibited both interleukin (IL)-2 gene transcription and IL-2 synthesis in stimulated T-cells.
Márquez et al., (2004) found that CAPE specifically inhibited both interleukin (IL)-2 gene transcription and IL-2 synthesis in stimulated T-cells.
Takagi et al., (2005) found that cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate.
Takagi et al., (2005) found that cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate.
activated macrophages in association with the secondary T-lymphocyte activation increased IFN-gamma production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.
Blonska et al., (2004) indicated that EEP exerts its inhibitory effect on the IL-1beta and iNOS gene expression in J774A.1 macrophages at the transcriptional level.
Blonska et al., (2004) indicated that EEP exerts its inhibitory effect on the IL-1beta and iNOS gene expression in J774A.1 macrophages at the transcriptional level.
Tested flavone derivatives contribute to the anti-inflammatory activity of propolis.
The cytokine, IL-2, IL-4 and IFN-gamma were significantly increased at the dose of 20 mg/kg CAPE group.
These results suggest that CAPE could have immunomodulatory effects in vivo (Park et al., 2004).
Bee venom contains a number of powerful anti-inflammatory substances, including adolapin and melittin.
Bee venom contains a number of powerful anti-inflammatory substances, including adolapin and melittin.
It is to be a hundred times more powerful than hydrocortisone,
melittin stimulates the body production of cortisol, a natural steroid that also acts as an anti-inflammatory.
Its 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.
Its 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.
Moon et al., (2007) demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia
Moon et al., (2007) demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia
They suggested that these compounds may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.
Mellitin had no effect on IL-1beta- or TNF-alpha-induced MMP1 or MMP3 production and did not decrease LPS-induced secretion of MMP1.
Mellitin had no effect on IL-1beta- or TNF-alpha-induced MMP1 or MMP3 production and did not decrease LPS-induced secretion of MMP1.
Among the serum proinflammatory cytokines, the production of TNF-alpha in the BV group was suppressed compared to the control group but IL-1beta was not suppressed.
in vivo bee venom treatment affects the production of IL-1 by macrophages directly (Hadjipetrou-Kourounakis and Yiangou, 1988).
in vivo bee venom treatment affects the production of IL-1 by macrophages directly (Hadjipetrou-Kourounakis and Yiangou, 1988).
Korean bee venom (KBV) has anti-inflammatory properties that inhibit NOS and TNF-α expression.
Korean bee venom (KBV) has anti-inflammatory properties that inhibit NOS and TNF-α expression.
KBV could be useful in inhibiting the production of inflammatory cytokine and NO production in neurodegenerative diseases (Han et al., 2007).
Hegazi et al., (2013) found that Propolis and bee venom are effective in treatment of psoriasis, with minimal tolerable side effects, when used either separately or in combination. a significant reduction in both PASI score and serum level of IL-1β was observed in all groups of patients.
Hegazi et al., (2013) found that Propolis and bee venom are effective in treatment of psoriasis, with minimal tolerable side effects, when used either separately or in combination. a significant reduction in both PASI score and serum level of IL-1β was observed in all groups of patients.
Correlation between percentage reduction of PASI score and that of IL-1 β showed a strong positive correlation in group I received bee venom.
Correlation between percentage reduction of PASI score and that of IL-1 β showed a strong positive correlation in group I received bee venom.
Continuous exposure of non-allergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion.
Continuous exposure of non-allergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion.
Meiler et al., (2008) found after multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells.
Meiler et al., (2008) found after multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells.
T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings.
Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production.
Kim et al., (2008) found that bee venom. injected i.p at doses of more than 20 microl/100g mouse once a day for 14 days
Kim et al., (2008) found that bee venom. injected i.p at doses of more than 20 microl/100g mouse once a day for 14 days
inhibited the ability of inguinal lymph node cells to produce
