Transfer Factor
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Transfer factors are essentially small immune messenger molecules that are produced by all higher organisms. Transfer factors were originally described as immune molecules that are derived from blood or spleen cells that cause
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
-specific
cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
, primarily delayed hypersensitivity and the production of
lymphokine Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte. They are protein mediators typically produced by T cells to direct the immune system response by signaling between its cells. Lymphokines have m ...
s, as well as binding to the antigens themselves. They have a molecular weight of approximately 5000
dalton Dalton may refer to: Science * Dalton (crater), a lunar crater * Dalton (program), chemistry software * Dalton (unit) (Da), the atomic mass unit * John Dalton, chemist, physicist and meteorologist Entertainment * Dalton (Buffyverse), minor cha ...
s and are composed entirely of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. Transfer factors were discovered by Henry Sherwood Lawrence in 1954. A second use of the term transfer factor applies to a likely different entity derived from cow colostrum or chicken egg yolk which is marketed as an oral
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
under the same name citing claims of benefit to the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
.


History

In 1942, Merrill Chase discovered that cells taken from the
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesoth ...
of Guinea pigs that had been immunized against an
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
could transfer immunity when injected into Guinea pigs that had never been exposed to the antigen; this phenomenon was the discovery of
cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
. Subsequent research attempted to uncover how the cells imparted their effects. Henry Sherwood Lawrence, in 1955, discovered that partial immunity could be transferred even when the immune cells had undergone
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
- indicating that cells did not need to be fully intact in order to produce immune effects. Lawrence went on to discover that only the factors less than 8000 daltons were required to transfer this immunity; he termed these to be "transfer factors". The history of cellular derived transfer factor as a treatment effectively ended in the early 1980s. While the research world was initially excited by the discovery of Dr. Lawrence and the possibility that a small molecule could affect the immune system, the concept of small molecules having such profound biologic effect had not been proven. Despite several successes in using transfer factor to treat human disease and uncover immune effects, one then-prominent researcher was exposed for falsifying data related to his work on transfer factor and guinea pigs; effectively casting all of transfer factor science in a negative light. This scandal was followed shortly thereafter by the discovery of the
Interleukin-1 alpha Interleukin-1 alpha (IL-1 alpha) also known as hematopoietin 1 is a cytokine of the interleukin 1 family that in humans is encoded by the ''IL1A'' gene. In general, Interleukin 1 is responsible for the production of inflammation, as well as the p ...
molecule and thus attention further shifted towards research on
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s. By 1973, it was discovered that blood products could harbor viruses such as
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
, indicating that transfer factor treatments derived from human or cow blood cells had the potential to transmit these diseases. With the eventual discovery of
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
as an additional
blood-borne disease A blood-borne disease is a disease that can be spread through contamination by blood and other body fluids. Blood can contain pathogens of various types, chief among which are microorganisms, like bacteria and parasites, and non-living infectious ...
most researchers viewed a product derived from blood as an unsafe treatment since screening for
hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...
and HIV/AIDS would not be developed until after 1985. Some studies using transfer factor have been conducted after the discovery of HIV/AIDS, but almost all have been outside of the United States. Most recently, transfer factor has been harvested from sources other than blood, and administered orally, as opposed to intravenously. This use of transfer factors from sources other than blood has not been accompanied by the same concerns associated with blood-borne diseases, since no blood is involved. Transfer factor based nutritional supplements have become extremely popular throughout the world. However the way transfer factor works is still not clear.


Scientific claims

To communicate between cells, the immune system employs hormone-like signal substances; transfer factors are one class of such immune system communication substances. Transfer factors include both inducer/helper functions (Inducer Factors) and regulator functions (Regulator Factors)—historically called "suppressor functions". The Inducer Factors translate an apparently mature immune response from the donor to the recipient. Regulator Factors help control overreactions and limit allergies and autoimmune conditions. Transfer factors have been shown to induce an immune response in less than 24 hours. Transfer factors are not species-specific, thus transfer factors produced by a cow's immune system are just as effective in humans as they are in the cow. Henry Sherwood Lawrence discovered that blood cells could 'transfer'
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
-specific
cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
even after the cells had undergone
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
. This lymphocyte product is sometimes referred to as "dialyzable leukocyte extract" in the scientific literature due to being an
extract An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts, h ...
from
white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s undergoing
dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
to remove all molecules larger than ~5000
dalton Dalton may refer to: Science * Dalton (crater), a lunar crater * Dalton (program), chemistry software * Dalton (unit) (Da), the atomic mass unit * John Dalton, chemist, physicist and meteorologist Entertainment * Dalton (Buffyverse), minor cha ...
s. Studies on cellular transfer factor have involved mostly animal models and small human clinical trials. These studies have demonstrated preliminary evidence of immune modulation as well as some clinical benefits in a handful of diseases, but the studies not been assessed beyond primary sources and the trials should only be considered pre-clinical. The exact identity (
protein primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...
) of the transfer factor is unknown.
HPLC High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
studies suggest that a common part in them is the fragment LLYAQD VDN, a sequence not found in any mammalian genomes.


Uses

Despite a small modicum of successes, transfer factor generated from human blood (human-derived), cow spleen (bovine-derived), or mouse spleen (murine derived) is not in routine clinical use today. A trial investigating its ability to
immunize Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-sel ...
children with
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
against
shingles Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
showed promise in a small number of patients, but represents only one of two
placebo-controlled studies Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed ...
. Instead, transfer factors derived from cow colostrum and/or chicken eggs yolks are used predominantly today.


Side effects


Colostrum-derived transfer factors

Long-term oral administration of colostrum-derived transfer factors has been shown to be safe.


Blood-derived transfer factors

Human-derived transfer factor appears to be safe for use for up to two years and bovine-derived cellular (from blood sources) transfer factor for up to three months. Side effects include
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
and swelling and pain at the injection site. Concern has been raised over the possibility of catching
Bovine spongiform encephalopathy Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of t ...
(Mad Cow Disease) or other diseases from animal blood-derived products. Transfer factors are contraindicated for women who are pregnant or breastfeeding. When human- and bovine-derived transfer factor are generated from
blood cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), ...
s they carry the potential for
blood-borne disease A blood-borne disease is a disease that can be spread through contamination by blood and other body fluids. Blood can contain pathogens of various types, chief among which are microorganisms, like bacteria and parasites, and non-living infectious ...
such as
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
and
Hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
.


Transfer factor (dietary supplement) history, claims, and side effects

Colostrum Colostrum, also known as beestings or first milk, is the first form of milk produced by the mammary glands of mammals (including humans) immediately following delivery of the newborn. Colostrum powder is rich in high protein and low in sugar and ...
is a form of milk produced by the
mammary glands A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in prima ...
of mammals (including humans) in late pregnancy. Colostrum also contains multiple immune modulating molecules, including high
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
levels. Based on studies noting an overlap in the observed
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
effects between a molecule contained in colostrum called
colostrinin Colostrinin (also known as CLN, proline-rich polypeptides or PRP) is a naturally occurring mixture of proline-rich polypeptides derived from colostrum. Early work on Colostrinin Colostrinin was originally identified by scientists working in Pol ...
and the dialyzable leukocyte extract mentioned above, a
hypothesis A hypothesis (plural hypotheses) is a proposed explanation for a phenomenon. For a hypothesis to be a scientific hypothesis, the scientific method requires that one can test it. Scientists generally base scientific hypotheses on previous obse ...
formed that the two were the same. There has been no recent research investigations comparing the two entities and thus there is no verifiable evidence that either colostrum or egg whites do or do not contain the cellular product that shares the name transfer factor. The orally available transfer factor is not obtained from humans nor from blood products of any mammal or animal and thus does not carry the presumed risks of contracting blood-borne or animal tissue derived diseases. Retailers of dietary supplement transfer factors advice against use by those with an organ transplant or women that are pregnant. Colostrum/egg derived transfer factors have been promoted as a treatment for a large number of diseases and health concerns but have not been proven effective in the treatment of any of these conditions. The
United States Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
regulates transfer factors as a dietary supplement and has issued a warning notice to a website selling transfer factors that they have not been proven to be effective or safe in the treatment of any condition, nor have there been any biological licenses or New Drug Applications produced for the substance.


See also

*
Lymphokine Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte. They are protein mediators typically produced by T cells to direct the immune system response by signaling between its cells. Lymphokines have m ...


References


External links

* {{Cytokines Immune system