Spirulina abstracts draft 6

Immunity
Zh Mikrobiol Epidemiol Immunobiol. 2001 Mar-Apr;(2):114-8.

[Biological activity of Spirulina]
[Article in Russian]

Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia.
In this review information of Spirulina platensis (SP), a blue-green alga
(photosynthesizing cyanobacterium) having diverse biological activity is
presented. Due to high content of highly valuable proteins, indispensable amino
acids, vitamins, beta-carotene and other pigments, mineral substances,
indispensable fatty acids and polysaccharides, PS has been found suitable for use
as bioactive additive. SP produces an immunostimulating effect by enhancing the
resistance of humans, mammals, chickens and fish to infections, the capacity of
influencing hemopoiesis, stimulating the production of antibodies and cytokines.
Under the influence of SP macrophages, T and B cells are activated. SP
sulfolipids have proved to be effective against HIV. Preparations obtained from
SP biomass have also been found active against herpesvirus, cytomegalovirus,
influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP
preparations are regarded as functional products contributing to the preservation
of the resident intestinal microflora, especially lactic acid bacilli and
bifidobacteria, and to a decrease in the level of Candida albicans. The biological
activity of SP with respect to microorganisms holds good promise for using these
microalgae as components of culture media.
Publication Types:
PMID: 11548244 [PubMed - indexed for MEDLINE] Int Immunopharmacol. 2002 Mar;2(4):423-34.

Activation of the human innate immune system by Spirulina:
augmentation of interferon production and NK cytotoxicity by oral
administration of hot water extract of Spirulina platensis.

Department of Immunology, Osaka Medical Center for Cancer and
Cardiovascular Diseases, Japan.
Spirulina platensis is a cyanobacterial species that is surmised to potentiate the
immune system leading to suppression of cancer development and viral infection.
Here, we identified the molecular mechanism of the human immune potentiating
capacity of Spirulina by analyzing blood cells of volunteers with pre and post oral
administration of hot water extract of Spirulina. NK functions represented by IFN
gamma production and cytolysis were enhanced after administration of Spirulina
in >50% subjects. IFN gamma was produced in an IL-12/IL-18-dependent
fashion. In vitro stimulation of blood cells with BCG cell wall skeleton (CWS)
allowed more potent IL-12 p40 production in cells from volunteers given
Spirulina than in cells without pre-exposure to Spirulina. As BCG-CWS serves as
a ligand for Toll-like receptor (TLR) 2 and 4 to raise the maturation stage of
monocytes/macrophages, Spirulina may be involved in the signaling responses
through Toll in blood cells even when orally administered. These observations
indicated that in humans Spirulina acts directly on myeloid lineages and either
directly or indirectly on NK cells. The presence of co-operative IL-12 and IL-18
is critically important for NK-mediated IFN gamma production.
Publication Types:
• Clinical Trial • Research Support, Non-U.S. Gov't PMID: 11962722 [PubMed - indexed for MEDLINE]
Enhancement of human adaptive immune responses by
administration of a high-molecular-weight polysaccharide extract
from the cyanobacterium Arthrospira platensis.

Department of Clinical Immunology and Blood Bank, Herlev Hospital, University
of Copenhagen, Herlev, Denmark. mortenlobner@hotmail.com
The effect of consumption of Immulina, a high-molecular-weight polysaccharide
extract from the cyanobacterium Arthrospira platensis, on adaptive immune
responses was investigated by evaluation of changes in leukocyte responsiveness
to two foreign recall antigens, Candida albicans (CA) and tetanus toxoid (TT), in
vitro. Consumption of Immulina by 11 healthy male volunteers caused an
immediate, but temporary, increase of CA-induced CD4+ T-helper (Th) cell
proliferation (P <.02). TT-induced Th cell proliferation was increased in
individuals over 50 years of age (P <.05) and correlated with age (P <.02).
Consumption for 8 days enhanced the CA-induced B cell proliferation (P <.02),
but after 56 days a diminution was seen (P <.03). The CA-elicited production of
the Th1 cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and
interferon (IFN)-gamma was increased after Immunlina administration for 3 days
(P <.001, <.03, and <.007, respectively), and increased IL-2 production
persisted after 56 days (P <.004). The TNF-alpha, IFN-gamma, and IL-6
responses to TT were enhanced after 8 and 14 days (P <.002-.05), while IL-5
responses increased significantly within 3 days (P <.04) and fell below baseline
levels after 14 days (P <.008). Conversely, consumption for 3 days inhibited the
IL-4 responses to both CA and TT (P <.008 and P <.03, respectively). No effects
on IL-10 responses were observed. Upon addition to normal mononuclear cells in
vitro, Immulina elicited strong TNF-alpha, IL-1beta, and IL-6 responses,
indicating that it acts by inducing a pro-inflammatory state. Taken together, the
data suggest that Immulina causes an age-dependent, temporary enhancement of
adaptive immune responses.
Publication Types:
PMID: 18598175 [PubMed - indexed for MEDLINE] J Nutr Sci Vitaminol (Tokyo). 2004 Apr;50(2):129-36.

Phycocyanin enhances secretary IgA antibody response and
suppresses allergic IgE antibody response in mice immunized with
antigen-entrapped biodegradable microparticles.
O.
Department of Health and Nutrition, Kagawa Nutrition University, Chiyoda,
Sakado, Saitama 350-0288, Japan.
In the present study, we have investigated the effects of phycocyanin, a biliprotein
of Spirulina platensis, on mucosal and systemic immune responses and allergic
inflammation in C3H/HeN and BALB/cA mice. To induce the antigen-specific
antibodies in the peripheral lymphoid tissues such as Peyer's patches and
mesenteric lymph nodes, biodegradable ovalbumin-entrapped poly (DL-lactide-
co-glycolide) particles were used as an antigen. Two weeks after the onset of
phycocyanin ingestion, mice were immunized with an aqueous ovalbumin (OVA)
solution. Starting at one week after the primary immunization, the mice were
subjected to oral immunization with the biodegradable OVA microparticles twice
a week. IgA, IgE and IgG1 antibodies were determined by ELISA. The OVA
microparticles of 4-microm diameter successfully induced antigen-specific
antibodies. In the mice that received phycocyanin treatment for 6 wk, a marked
increase in the antigen-specific, as well as the total, IgA antibody level was
observed in the Peyer's patches, mesenteric lymph nodes and intestinal mucosa as
well as in the spleen cells. Both antigen-specific IgG1 and IgE antibody levels in
the serum were suppressed by ingestion of phycocyanin for 8 wk. However,
inflammation of the small intestine, monitored as vascular permeability by the
Evans blue-leaking method was reduced by phycocyanin at 6 wk, which preceded
the suppression of antigen-specific IgG1 and IgE antibody production by 2 wk.
These results suggest that phycocyanin enhances biological defense activity
against infectious diseases through sustaining functions of the mucosal immune
system and reduces allergic inflammation by the suppression of antigen-specific
IgE antibody.
PMID: 15242017 [PubMed - indexed for MEDLINE]
Arch Biochem Biophys. 2007 Mar 15;459(2):169-77. Epub 2007 Jan 29.

C-Phycocyanin inhibits 2-acetylaminofluorene-induced expression
of MDR1 in mouse macrophage cells: ROS mediated pathway
determined via combination of experimental and In silico analysis.
P.
Department of Animal Sciences, School of Life Sciences, University of
Hyderabad, Hyderabad 500046, India.
We studied the effects of C-Phycocyanin (C-PC), a biliprotein from Spirulina
platensis on the 2-acetylaminofluorene (2-AAF)-induced expression of MDR1,
encoded by the multidrug resistance (MDR1) gene, in mouse macrophage cell line
(RAW 264.7). Our experimental and In silico studies revealed a significant
inhibition of 2-AAF-induced expression of MDR1 protein in C-PC treated mouse
macrophage cell line. MDR1 induction by 2-AAF was dependent on ROS
(reactive oxygen species)-Akt (protein kinase B)-NF-kappaB (Nuclear factor
kappa B) signaling pathway. Generation of ROS, phosphorylation of Akt and
corresponding nuclear translocation of NF-kappaB, the events that play a major
role in the induction of MDR1 expression, were decreased significantly in C-PC
treated cells. NADPH oxidase inhibitor, DPI (Diphenyl iodide), and
pharmacological inhibitor of Akt, Akt inhibitor IV, also showed a reduction in
MDR1 expression, although not to the same extent as C-PC mediated inhibition
of MDR1 expression. To further understand the mechanism, we created a
computational model of the detailed ROS-Akt-NF-kappaB pathway. C-PC was
modeled purely as a ROS scavenger and this representation matched the
experimental trends accurately. Also the ROS levels determined through In silico
investigation showed that C-PC was more effective in reduction of MDR1
expression than inhibitors of NADPH oxidase and Akt. Our experimental and In
silico studies collectively suggest that 2-AAF induces MDR1 by ROS dependent
pathway and C-PC is a potential negative regulator of MDR1 expression. This
down regulation of MDR1 expression, induced by xenobiotics such as 2-AAF,
suggests C-PC's usefulness in overcoming the drug resistance in cellular systems.
Publication Types:
PMID: 17303067 [PubMed - indexed for MEDLINE] Zh Mikrobiol Epidemiol Immunobiol. 1979 Dec;(12):75-9.
[Immunostimulating activity of the lipopolysaccharides of blue-
green algae]
[Article in Russian]

The whole cells of blue-gree algae and lipopolysaccharides isolated from these
cells were shown to stimulate the production of macro-(mainly) and
microglobulin antibodies in rabbits. The macro- and microphage indices in rabbits
increased significantly after the injection of LPS isolated from blue-green algae
24--48 hours before infecting the animals with a virulent Y. pseudotuberculosis
strain. Besides, the inhibiting action of this strain on the migration of phagocytes
to the site of infection was abolished immediately after the injection. The use of
the indirect hemagglutination test allowed to prove the absence of close antigenic
interrelations between blue-green algae and the following organisms: Spirulina
platensis, Microcystis aeruginosa, Phormidium africanum and P. uncinatum.
Publication Types:
PMID: 117655 [PubMed - indexed for MEDLINE]
[Studies of immunomodulation caused by selenium-enriched
phycocyanin]
[Article in Russian]

An influense was studied in rats of selenium enriched phycocyanin (Se-PC) from
food microalgae Spirulina on anaphylactic reaction severity and circulating
antibody response against model allergen--hen's egg white ovalbumin. Se-PC was
introduced into diet in form of protein isolate precipitated with ammonia sulphate.
Se-PC dosage made up to 450 mcg per rat daily that corresponded to 5 mcg of
selenium. There were no differences revealed between experimental and control
group that received standard diet in severity of anaphylactic reaction.
Nevertheless rats receiving Se-PC demonstrated significantly increased specific
IgG response. The probable immunomodulating properties of Se-PC included into
food are discussed.
Publication Types:
PMID: 16729754 [PubMed - indexed for MEDLINE] Immunopharmacol Immunotoxicol. 2001 May;23(2):281-9.
Enhancement of chicken macrophage phagocytic function and
nitrite production by dietary Spirulina platensis.
Al-Batshan HA, Al-Mufarrej SI, Al-Homaidan AA, Qureshi MA.
Department of Animal Production, College of Agriculture, King Saud University,
Riyadh, Kingdom of Saudi Arabia.
The effects of dietary Spirulina platensis on chicken macrophage phagocytic
function and nitrite production were examined. Day old broiler (meat-type) chicks
were randomly assigned to various pens of electrically heated wire batteries.
Dietary treatment groups included a basal diet with no dietary Spirulina added,
and three additional groups with 0.5, 1.0 and 2.0% dietary Spirulina. Feed and
water were provided for ad libitum consumption from one day of age. Sephadex-
elicited macrophages were harvested at 14, 35 and 42 days of age. Phagocytosis
assay was performed by co-incubating sheep red blood cells (SRBC) with the
adherent macrophage monolayers. For nitrite quantification, macrophage cultures
from various dietary treatment groups were stimulated in the presence or absence
of 1 microg/mL of Escherichia coli lipopolysaccharide. These culture supernatant
fractions were then tested for nitrite levels using the Greiss reagent technique. All
Spirulina dietary group macrophages exhibited an enhanced phagocytic activity in
terms of overall phagocytic percentage (range = 28 to 39% versus 24 to 25% in
the basal group) and the average number of SRBC per phagocytic macrophage
(range = 2.2 to 3.6 versus 1.8 to 2.5 in the basal group). This increase was linear
with each incremental increase of dietary Spirulina. While LPS-induced nitrite
levels in macrophages from basal diet group ranged from 60 to 278 microM over
the three developmental ages, these levels in all Spirulina dietary groups were
significantly higher (0.5% group range = 198 to 457 microM; 1.0% group range =
161 to 359 microM and 2.0% group range = 204 to 420 microM. These data
clearly show that Spirulina platensis feeding upregulates macrophage phagocytic
as well as metabolic pathways leading to increased nitric oxide synthase activity.
These findings therefore imply that Spirulina platensis may enhance the functions
of mononuclear phagocytic system thereby increasing the disease resistance
potential in chickens.
Publication Types:
• In Vitro • Research Support, Non-U.S. Gov't • Research Support, U.S. Gov't, Non-P.H.S. PMID: 11417854 [PubMed - indexed for MEDLINE]
Effect of spirulina on the secretion of cytokines from peripheral
blood mononuclear cells.
Mao TK, VAN DE Water J, Gershwin ME.
ABSTRACT The purpose of this study was to evaluate the immunomodulatory
activity of Spirulina, a bluegreen alga used as a food supplement. The effects of
Spirulina on the secretion of three cytokines from unstimulated and stimulated
human peripheral blood mononuclear cells (PBMC) were examined. In resting
PBMC, Spirulina stimulated secretion of interleukin (IL)-1beta, IL-4, and
interferon (IFN)-gamma to nearly 2.0, 3.3, and 13.6 times basal levels,
respectively. Spirulina induced levels of IFN-gamma (229 +/- 104 pg/ml) that
were comparable to those seen after phytohemagglutinin (PHA) stimulation (476
+/- 121 pg/ml). However, it was much less mitogenic than PHA (13.1 +/- 6.9
pg/ml) with respect to the induction of IL-4 secretion (0.34 +/- 0.1 pg/ml). In
PHA-stimulated cells, Spirulina enhanced secretion of IL-1beta, IL-4, and IFN-
beta by 2.9, 4.0., and 1.6 times, respectively. Although Spirulina stimulates
several cytokines, it is clearly more effective in the generation of a Thl-type
response. This in vitro study offers additional data for consideration of the
potential therapeutic benefits of Spirulina.
PMID: 19281334 [PubMed - in process]

[Evaluation of the efficacy of a plant adaptogen (spirulina) in the
pathognic therapy of primary tuberculosis in children]
[Article in Ukrainian]
Kostromina VP, Derkach OV, Symonenkova NV, Riechkina OO,
Otroshchenko AO.
The use of spirulina and its efficiency have been studied in a comparative aspect
as a systemic biocorrector, in a combined treatment of tuberculosis in 26 children.
It has been ascertained that application of spirulina as a pathogenetic means of
remediation permits shortening the intoxication syndrome regression time,
reducing the frequency of adverse reactions in administering antituberculous
preparations.
Publication Types:
• Clinical Trial • Comparative Study • English Abstract PMID: 14618819 [PubMed - indexed for MEDLINE]
Isolation of three high molecular weight polysaccharide
preparations with potent immunostimulatory activity from
Spirulina platensis, aphanizomenon flos-aquae and Chlorella
pyrenoidosa.
Pugh N, Ross SA, ElSohly HN, ElSohly MA, Pasco DS.
Department of Pharmacognosy, School of Pharmacy, University of Mississippi,
University, Mississippi 38677, USA.
This research describes the identification of three new high molecular weight
polysaccharide preparations isolated from food-grade microalgae that are potent
activators of human monocytes/macrophages: "Immulina" from Spirulina
platensis, "Immunon" from Aphanizomenon flos-aquae, and "Immurella" from
Chlorella pyrenoidosa. These polysaccharides are structurally complex and have
estimated molecular weights above ten million daltons. All three polysaccharides
are highly water soluble and comprise between 0.5 % and 2.0 % of microalgal dry
weight.Immunostimulatory activity was measured using a transcription factor-
based bioassay for nuclear factor kappa B (NF-kappa B) activation in THP-1
human monocytes/macrophages. Using this system the EC(50) values for these
microalgal polysaccharides are between 20 and 110 ng/ml (about 10pM). THP-1
activation was confirmed by measuring immune cytokine mRNA induction using
reverse transcriptase-polymerase chain reaction (RT-PCR). Each polysaccharide
substantially increased mRNA levels of interleukin-1beta (IL-1beta) and tumor
necrosis factor-alpha (TNF-alpha). These polysaccharides are between one
hundred and one thousand times more active for in vitro monocyte activation than
polysaccharide preparations that are currently used clinically for cancer
immunotherapy.
Publication Types:
• Research Support, U.S. Gov't, Non-P.H.S. PMID: 11731916 [PubMed - indexed for MEDLINE] Biochim Biophys Acta. 1997 Mar 1;1355(3):241-7.
Calcium spirulan as an inducer of tissue-type plasminogen activator
in human fetal lung fibroblasts.
Hayakawa Y, Hayashi T, Hayashi K, Ozawa T, Niiya K, Sakuragawa N.
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama,
Japan. hayakawa@ms.toyama-mpu.ac.jp
Calcium spirulan (Ca-SP), a novel sulfated polysaccharide isolated from the blue-
green alga Spirulina platensis, has been found to have antiviral and heparin
cofactor II-dependent antithrombin activities. We have obtained evidence that Ca-
SP is a potent inducer of tissue-type plasminogen activator (t-PA) production. The
addition of Ca-SP to a culture of IMR-90 human fetal lung fibroblasts increased t-
PA concentrations in the conditioned medium, in a dose- and time-dependent
manner, but in the cell lysate, t-PA concentrations were unchanged, suggesting
that t-PA induced by Ca-SP is easily secreted into the conditioned medium. The
amount of newly synthesized t-PA in IMR-90 cells, as measured by labeling with
[35S]methionine and subsequent immunoprecipitation of t-PA from conditioned
medium, was significantly increased by Ca-SP-stimulation. However, Ca-SP did
not increase the t-PA mRNA levels. As previously reported, thrombin stimulated
t-PA gene transcription in IMR-90 cells, and the simultaneous treatment with Ca-
SP and thrombin caused further enhancement of t-PA production, in a synergistic
manner. It would thus appear that Ca-SP increases t-PA production through post-
transcriptional processes. IMR-90 cells also produce plasminogen activator
inhibitor type-1 (PAI-1), but Ca-SP showed little effect on the PAI-1 production.
H-SP, which was obtained by removing the calcium from Ca-SP, had no effect on
the t-PA production. Na-SP, which was prepared by replacement of the calcium
with sodium, stimulated the t-PA production similarly to Ca-SP. Thus, Ca-SP
specifically induces t-PA production, and the molecular conformation of Ca-SP
maintained by Ca or Na may be essential for the stimulation of t-PA synthesis.
PMID: 9060995 [PubMed - indexed for MEDLINE]
Immunopharmacol Immunotoxicol. 1996 Aug;18(3):465-76.
Dietary Spirulina platensis enhances humoral and cell-mediated
immune functions in chickens.
Qureshi MA, Garlich JD, Kidd MT.
Department of Poultry Science, North Carolina State University, Raleigh 27695-
7608, USA.
Cornell K-strain White Leghorns and broiler chicks were raised to 7 wks and 3
wks of age respectively, with diets containing various levels (0, 10, 100, 1,000
and 10,000 ppm) of Spirulina platensis from day of hatch. Chicks in all treatment
groups had comparable body weights. While bursal and splenic weights did not
change, the K-strain chicks had larger thymuses (P < or =.05) over the controls (0
ppm group). No differences were observed in anti-sheep red blood cells
antibodies during primary response. However, during secondary response, K-
strain chicks in all Spirulina-dietary groups had higher total anti-SRBC titers with
10,000 ppm group being the highest (6.8 Log2) versus the 0 ppm (5.5 Log2)
group. In broiler chicks, a one Log increase in IgG (P < or =.05) was observed in
10,000 ppm group over the controls. Similarly, chicks in 10,000 ppm Spirulina
group had a higher PHA-P-mediated lymphoproliferative response over the 0 ppm
controls. Macrophages isolated from both K-strain (10,000 ppm group) and
broilers from all Spirulina groups had higher phagocytic potential than the 0 ppm
groups. Spirulina supplementation at 10,000 ppm level also increased NK-cell
activity by two fold over the controls. These studies show that Spirulina
supplementation increases several immunological functions implying that a
dietary inclusion of Spirulina at a level of 10,000 ppm may enhance disease
resistance potential in chickens.
PMID: 8872497 [PubMed - indexed for MEDLINE]
Immunopharmacol Immunotoxicol. 1996 Aug;18(3):457-63.
Spirulina platensis exposure enhances macrophage phagocytic
function in cats.
Qureshi MA, Ali RA.
Department of Poultry Science, North Carolina State University, Raleigh 27695-
7608, USA.
Bronchoalveolar lavage macrophages isolated from cats were cultured on glass
coverslips. Macrophages were exposed to a water-soluble extract of Spirulina
platensis in concentration range of 0 to 60 micrograms per mL for two hours.
Spirulina-extract exposure did not cause significant macrophage cytotoxicity over
untreated control cultures. Macrophage monolayers from treated and control
cultures were incubated with sheep red blood cells (SRBC) as well as viable
Escherichia coli. The percentages of phagocytic macrophages for both of these
particulate antigens were higher (a two-fold increase in SRBC phagocytosis and
over 10% increase in Escherichia coli uptake) in cultures treated with various
concentrations of Spirulina-extract. However, the numbers of either types of
particles internalized by phagocytic macrophage were not different between the
control and treated cultures. These data which showed that Spirulina platensis
extract enhances macrophage phagocytic function imply that dietary Spirulina
supplementation may improve the disease resistance potential in cats.
PMID: 8872496 [PubMed - indexed for MEDLINE]
J Nutr Sci Vitaminol (Tokyo). 1994 Oct;40(5):431-41.
Enhancement of antibody production in mice by dietary Spirulina
platensis.
Hayashi O, Katoh T, Okuwaki Y.
Department of Health and Nutrition, Kagawa Nutrition University, Sakado, Japan.
Mice fed a Spirulina platensis diet showed increased numbers of splenic antibody-
producing cells in the primary immune response to sheep red blood cells (SRBC).
However, immunoglobulin G (IgG)-antibody production in the secondary
immune response was hardly affected. The percentage of phagocytic cells in
peritoneal macrophages from the mice fed S. platensis diet, as well as the
proliferation of spleen cells by either concanavalin A (Con A) or
phytohemagglutinin (PHA) was significantly increased. Addition of a hot-water
extract of S. platensis (SHW) to an in vitro culture of spleen cells markedly
increased proliferation of these cells, whereas culture of thymus cells was scarcely
affected. The Spirulina extract also significantly enhanced interleukin-1 (IL-1)
production from peritoneal macrophages. Addition to the in vitro spleen cell
culture of SHW as well as the supernatant of macrophages stimulated with SHW
resulted in enhancement of antibody production, that is, an increase of the number
of PFC. These results suggest that Spirulina enhances the immune response,
particularly the primary response, by stimulating macrophage functions,
phagocytosis, and IL-1 production.
PMID: 7891204 [PubMed - indexed for MEDLINE]
Phytother Res. 2004 Sep;18(9):754-7.

Antibacterial activity of volatile component and various extracts of
Spirulina platensis.
Ozdemir G, Karabay NU, Dalay MC, Pazarbasi B.
Ege University, Faculty of Science, Department of Biology, 35100 Bornova,
Izmir, Turkey. gozdemir@sci.ege.edu.tr
The methanol, dichloromethane, petroleum ether, ethyl acetate extracts and
volatile components of Spirulina platensis were tested in vitro for their
antimicrobial activity (four Gram-positive, six Gram-negative bacteria and
Candida albicans ATCC 10239). GC-MS analysis of the volatile components of
S. platensis resulted in the identification of 15 compounds which constituted
96.45% of the total compounds. The volatile components of S. platensis consisted
of heptadecane (39.70%) and tetradecane (34.61%) as major components. The
methanol extract showed more potent antimicrobial activity than
dichloromethane, petroleum ether, ethyl acetate extracts and volatile components.
Copyright (c) 2004 John Wiley & Sons, Ltd.
Publication Types:
PMID: 15478198 [PubMed - indexed for MEDLINE]
[The influence of Spirulina and Selen-Spirulina on some indexes of
rat's immune status]
[Article in Russian]
Trushina EN, Gladkikh O, Gadzhieva ZM, Mustafina OK, Pozdniakov AL.
This paper reviews evidence for the immune-enhancing effect of Spirulina (Sp)
and Selen-Spirulina (Se-Sp) in male Wistar rats. The rats of control group fed
half-synthetic diet. Rats of experimental groups consumed the half-synthetic diets
with Sp (10 g/kg diet) or Se-Sp (350 microg Se/kg diet) for 2 weeks. Using rats
lymphocytes in vitro after phytohemagglutinin stimulation was demonstrated that
lymphocytes from Sp and Se-Sp groups secreted of interleukin-2 and interferon-
gamma more control group. Induction of interleukin-4 was comparable with once
of control group. We believed that Sp and Se-Sp are more effective in stimulating
a Th-1--type response and hence potentiates cell-mediated immunity. The
immunostimulatory effect of Sp and Se-Sp was confirmed by morphologic and
morphometric investigation of rats spleen, also with by NBT-test of peritoneal
macrophages.
Publication Types:
• Comparative Study • English Abstract PMID: 17561650 [PubMed - indexed for MEDLINE] Int Immunopharmacol. 2006 Dec 5;6(12):1808-14. Epub 2006 Aug 28.

Toll-like receptor 2-dependent activation of monocytes by Spirulina
polysaccharide and its immune enhancing action in mice.
Balachandran P, Pugh ND, Ma G, Pasco DS.
National Center for Natural Products Research, Research Institute of
Pharmaceutical Sciences, School of Pharmacy, University of Mississippi,
University, MS 38677, USA.
We reported previously that a high molecular weight polysaccharide fraction
(Immulina) from Spirulina was a potent activator of NF-kappa B and induced
both IL-1 beta and TNF-alpha mRNAs in THP-1 human monocytes. In the
present study, we show that NF-kappa B activation by Immulina is suppressed by
antibodies to CD14 and TLR2 but not by antibodies to TLR4. Similarly, NF-
kappa B directed luciferase expression was enhanced by Immulina treatment
when cells were co-transfected with vectors expressing proteins supporting
TLR2- (CD14 and TLR2) but not TLR4-(CD14, TLR4, and MD-2) dependent
activation. Mice that consumed a chemically defined chow mixed with an extract
containing Immulina exhibited changes in several immune parameters. The ex
vivo production of IgA and IL-6 from Peyer's patch cells was enhanced 2-fold and
interferon-gamma production from spleen cells was increased 4-fold in Immulina-
treated mice. The enhanced production of these factors was most notable with
mice that had consumed this extract for 4 or 5 days. These studies shed light on
how Immulina activates cells of the innate immune system and suggests that oral
consumption of this polysaccharide can enhance components within both the
mucosal and systemic immune systems.
Publication Types:
• Research Support, Non-U.S. Gov't • Research Support, U.S. Gov't, Non-P.H.S. PMID: 17052671 [PubMed - indexed for MEDLINE] J Altern Complement Med. 2006 Jun;12(5):429-35.

Immolina, a high-molecular-weight polysaccharide fraction of
Spirulina, enhances chemokine expression in human monocytic
THP-1 cells.
Grzanna R, Polotsky A, Phan PV, Pugh N, Pasco D, Frondoza CG.
RMG Biosciences, Inc., Baltimore, MD, USA.
INTRODUCTION: Spirulina (Spirulina platensis) is a dietary supplement valued
for its immune-enhancing properties. We previously reported that the
immunostimulatory effect of spirulina can be traced to a high-molecular- weight
polysaccharide fraction. This fraction, labeled Immolina, activates nuclear factor
kappa-B in human monocytic THP-1 cells and increases expression of
proinflammatory cytokines. OBJECTIVE: To characterize further the
immunostimulatory effects of Immolina on THP-1 cells, we evaluated its effect
on genes encoding the chemokines interleukin (IL)-8, MCP-1, MIP-1alpha, MIP-
1beta, IP-10, the cytokines tumor necrosis factor (TNF)-alpha, IL-1beta, and the
enzyme cyclo-oxygenase-2 (COX-2). METHODS: THP-1 cells were exposed to
concentrations of Immolina ranging from 1 ng/mL to 100 microg/mL and changes
in gene expression were assessed by reverse transcriptase-polymerase chain
reaction (RT-PCR). For comparison, THP-1 cells were activated with 1 ng/mL of
TNF-alpha, 10 ng/mL of IL-1beta, or 10 ng/mL of lipopolysaccharide using the
same assay conditions. To assess the response of THP-1 cells to Immolina at the
protein level, we probed culture supernatants using a cytokine array immunoblot
assay. RESULTS: RT-PCR analysis revealed that Immolina dose-dependently
increased the expression of all 5 chemokines tested as well as the expression of
TNF-alpha, IL-1beta, and COX-2. The cytokine array immunoblot assay revealed
an increase in the chemokines IL-8 and MIP-1beta. Thymidine uptake
experiments verified that Immolina did not affect the viability and growth rate of
THP-1 cells. CONCLUSIONS: The results of the experiments demonstrate that
Immolina activates THP-1 cells in a manner that is consistent with the recruitment
of diverse populations of leukocytes in response to inflammatory and infectious
signals.
Publication Types:
• Research Support, Non-U.S. Gov't • Research Support, U.S. Gov't, Non-P.H.S. PMID: 16813506 [PubMed - indexed for MEDLINE] Nat Med (Tokyo). 2009 Apr;63(2):169-75. Epub 2008 Dec 18.

Appraisal of immunomodulatory potential of Spirulina fusiformis:
an in vivo and in vitro study.
Rasool M, Sabina EP.
Faculty of Heath and Life Sciences, Management and Science University,
Sekysen 13, Shah Alam, Selangor Darul Ehsan, Malaysia. mkr474@gmail.com
In recent years, Spirulina has gained more and more attention from medical
scientists as a nutraceutical and a source of potential pharmaceuticals. The present
study was conducted to elucidate the immunomodulatory effect of Spirulina
fusiformis (a cyanobacterium of the family Oscillatoriaceae) in vivo and in vitro.
The in vivo effect of S. fusiformis (400 or 800 mg/kg body wt.) on humoral
immune response, cell-mediated immune response and tumour necrosis factor
alpha was investigated in mice. We also evaluated the effect of S. fusiformis (50
or 100 microg/ml) in vitro on mitogen (phytohaemagglutinin)-induced T
lymphocyte proliferation in heparinized human peripheral blood. For comparison,
dexamethasone was used as a standard. In mice, S. fusiformis (400 or 800 mg/kg
body wt.) administration significantly inhibited the humoral immune response,
cell-mediated immune response (delayed-type hypersensitivity reaction (DTH))
and tumour necrosis factor alpha in a dose-dependent manner. In vitro, S.
fusiformis (50 or 100 microg/ml) decreased the mitogen (phytohaemagglutinin)-
induced T lymphocyte proliferation in a concentration-dependent manner when
compared with control cells. These observations clearly suggest that S. fusiformis
has a remarkable immunosuppressive effect, which provides a scientific
validation for the popular use of this drug, and helped us in further work on
investigating its complete mechanism of action.
Publication Types:
• Comparative Study • Research Support, Non-U.S. Gov't PMID: 19093070 [PubMed - indexed for MEDLINE] Evid Based Complement Alternat Med. 2008 Sep 14. [Epub ahead of print]
Spirulina in Clinical Practice: Evidence-Based Human Applications.
Karkos PD, Leong SC, Karkos CD, Sivaji N, Assimakopoulos DA.
Specialist Registrar in Otolaryngology, 36 Hopkinsons Court, Walls Avenue,
Chester CH1 4LN, UK. E- pkarkos@aol.com.
Spirulina or Arthrospira is a blue-green alga that became famous after it was
successfully used by NASA as a dietary supplement for astronauts on space
missions. It has the ability to modulate immune functions and exhibits anti-
inflammatory properties by inhibiting the release of histamine by mast cells.
Multiple studies investigating the efficacy and the potential clinical applications
of Spirulina in treating several diseases have been performed and a few
randomized controlled trials and systematic reviews suggest that this alga may
improve several symptoms and may even have an anticancer, antiviral and
antiallergic effects. Current and potential clinical applications, issues of safety,
indications, side-effects and levels of evidence are addressed in this review. Areas
of ongoing and future research are also discussed.
PMID: 18955364 [PubMed - as supplied by publisher]

Source: http://www.marcusrohrerspirulina.at/files/7013/0026/2667/Immunity.pdf