A Review of immunomodulators with reference to Canova - Similima

A Review of
immunomodulators with
reference to Canova
E.Smit, H.Moberholzer & E.Pretorius
Dept of Anatomy, University of Pretoria,
S. Africa
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Immunomodlator – Substances which modify the immunity
of an individual to favour a particular immunological response
Canova – A Homoeopathic product produced according to
Hahnemanian homoeopathic method in Brazil
Its role in Carcinoma, Haematopoesis, Macrophage &
Monocyte activation, its ability to stabilize platelet morphology
in AIDS is reviewed
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Introduction
Immunity is the reaction of cells & tissues to foreign
substances / Pathogens
Immune response requires timely interplay of multiple cell
types with in specific microbiological environment to
maintain immune homeostasis
Innate – First encounter to a pathogen ( Inborn)
Contributed by Neutrophil, Monocyte & Macrophage
Adaptive / Acquired – Consequences of an initial exposure
( Developed). Contributed by B & T Lymphocytes &
Cytokines
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Immunomodulators – Agents to enhance a particular
immunological response available as TLR ( Toll like receptors),
Cytokines, Cytokine receptors, Transcription factor modulation,
Cell surface molecule, T H subset balance, Signalling sequence
& gene activation
1) Specific to pathogen – Includes Ab reagents & Vaccines
2) Non specific – Includes Cytokine, Antimicrobial peptide,
Antimicrobial drugs & microbe (Probiotics)
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Immune response
Ag presenting cells ( Dendritic cells, Monocytes, Macrophage)
at the site of entry of microbes ( Skin, GIT, Respi) capture Ag of
microbe by phagocytosis / pinocytosis
Move to T cell rich lymph node with the help of cytokines
(IL,TNF) produced by sorrounding cells
During migration they mature & start to express MHC (Major
histocompatibilty complex) which display Ag to the cells
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� T Lymphocytes (Helper) stimulate B Lymphocytes to
produce Ab which are recognized by phagocytes
Endocytosis / pinocytosis
Fuses to lysosome
Ag are digested by proteolytic enzymes to peptides
� Ag recognized by CD8 & T cells Cytotoxic T cells
which kill infected cells with foreign Ag
� T cells secrete cytokines when recognizes the co stimulators
on APC (Ag presenting cells) Proliferation &
differentiation of T cells
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Human MHC proteins – HLA decided by gene on Chr 6
(A ,B,C – class I DP, PQ, DR – ClassII)
Each bind preferentially to different Antigenic peptides
Responsible for Variation in immune responsiveness to
particular Ag in different individual
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TLR ‘s are recognition receptors that are activated by
specific components, microbes & certain host molecules
13 mamallian TLR’s which can be activated by pathogens
(Exogenous) & immune related (endogenous) are
identified
An Ag when taken up by an APC, the TLR ‘s are stimulated
Increase MHC Ag & cytokine production
Stimulate other APC’s & T & B Lymphocytes
Proper immune response
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Immunomodulatory therapies involve one / multiple TLR’s
� Lipid A component of lipopolysacharride is a TLR agonist
that induce Th 1 response
� By blocking / stimulating TLR’s, a modification Th1 / Th2
cytokine balance can effect various immunological status
TLR 9 – Allergic disease
CpG – Infectious disease like Hepatitis B, C, Anthrax ,
influenza, Ca, Melanoma
(In combination with chemotherapy / adjuvant)
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Cytokines are diverse family of polypeptide hormone & growth
factor that regulate many cellular processes produced by
variety of immune cells to communicate & orchestrate an
immune attack
Modulation of cytokine secretion may offer novel approaches
in treatment of various diseases
Done by implementation of antiinflammatory cytokines
(IF,IL 4,GF) / neutralizing proinflammatory cytokines ( IL 2, IF
gamma, TNF)
IL - Used in treatment of RA ( Prevents interaction of IL1 to its
cell surface receptors)
TNF – RA, Crohn’s disease, Psoriasis ( AI )
INF alpha – advanced melanoma
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One of the key concept of homoeopathy is stimulation of
body’s defense mechanisms in the process to prevent / treat
illness
In the process of succussion there is an antigenic imprinting of
the crystalline lattice of water even though no single molecule /
molecular remnant of of original substance is present
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CANOVA is a homoeopathic product developed & produced
according to Hahnemanian method as a homoeopathic
remedy in Brazil
Contains –Thuja, Bryonia, Aconite, Arsenic Alb & Lachesis
No toxicity / mutagenic effects have been reported
Available as drops in concentration ranging from 4% to 50%
50ml contains 49.965ml water & 0.035ml alcohol
Researchers have found that it stimulates host defense in
pathological states
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Invitro study of canova on BM cells showed activation
Invivo & invitro study with canova showed activation of
macrophages, enhanced spreading of cells & formation of
microvillous extrusions
Activation of Monocytes, differentiation to macrophages with
increased expression of CD8
Like cytokine, Canova induces differentiation of monocytes
immunomodulatory activity
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In sarcoma - Canova treated mice showed delay in
development & reduction in size of the tumor, increased
infiltration of lymphoid cells, GT & fibrosis sorrounding the
tumor, Leucocytosis & Lymphocytosis ( enhanced immune
response) compared to control group
Macrophages showed 86% activation in Canova treated & 15%
activation in control
TNF alpha production was decreased while IL2 & IFN gamma
revealed no difference with control group
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Leishmania – Reduced infection & decreased parasite load in
regional LN & spleen (in vivo)
Canova caused indirect proliferation of lymphocytes
(Thro’activated macrophages)
Increases Leucocytes, number of CD4 T lymphocytes, NK
cells in peripheral blood
Increase in no. of adherent, larger & activated cells in canova
treated group.
HIV – Less morphological changes in platelet, less pronounced
membrane blebbing ( prevents thrombocytopenia)
Protects membranes of platelets & thereby immune system by
protecting ultrastructure
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Conclusion
Canova is a complex homoeopathic remedy used as
immunomodulator
It activates macrophages, stimulates differentiation &
modulates other inflammatory process
More research is needed to expand the possible uses &
application of homoeopathic immunomodulator
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Immunomodulators
Homoeopathic medicines act by immunomodulating ?.......
Homoeopathic medicine given in other countries
Only succussions - Homoeopathic preparation
Different dilutions – 4%, 50% etc
Mixing – Should we try?
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