Freund's adjuvant
Encyclopedia
Freund's adjuvant is a solution of antigen
emulsified in mineral oil
and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant,(CFA or FCA) is composed of inactivated and dried mycobacteria
(usually M. tuberculosis
), whereas the incomplete form (IFA or FIA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T. Freund
.
and may lead to the potentiation of the production of certain immunoglobulins, but this effect depends on the animal model
used. Its use in humans is forbidden by regulatory authorities, due to its toxicity
. Even for animal research there are currently guidelines
associated with its use, due to its pain
ful reaction and potential for tissue damage. Injections of CFA should be subcutaneous or intraperitoneal, because intradermal injections may cause skin ulceration and necrosis
; intramuscular injections may lead to temporary or permanent muscle
lesion, and intravenous injections may produce pulmonary lipid embolism
.
and combined with prepared spleen cells was said to have reversed it. In 2006 these claims were challenged by the findings of several other researchers. Although newspapers have described the 2006 findings as confirming the earlier experiments, in substantial ways they conflict with them. A report from NIH
was released on November 23, 2006 in Science
confirming the participation of spleen cells in reversing end-stage diabetes.
It has also been investigated in an animal model of Parkinson's disease
.
, which is thought to kill the T-cells responsible for the autoimmune destruction of the pancreatic Beta cells. Still in question is whether the regrowth of functional insulin
-producing cells occurs due to differentiation and proliferation
of existing pancreatic
stem cells, or whether the injected spleen cells re-differentiate to an insulin-producing form. Denise Faustman
, whose work has been central to developing the protocol, has suggested that both mechanisms may play a role. However, in experiments to verify and examine her work, Suri reported that DNA-based evidence yielded no sign of spleen cell derivatives in pancreatic islet
Beta cells analyzed after treatments.
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
emulsified in mineral oil
Mineral oil
A mineral oil is any of various colorless, odorless, light mixtures of alkanes in the C15 to C40 range from a non-vegetable source, particularly a distillate of petroleum....
and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant,(CFA or FCA) is composed of inactivated and dried mycobacteria
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...
(usually M. tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
), whereas the incomplete form (IFA or FIA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T. Freund
Jules T. Freund
Jules T Freund was an Hungarian-born American immunologist.-See also:* Freund's adjuvant...
.
Regulation
Freund's complete adjuvant is effective in stimulating cell-mediated immunityCell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
and may lead to the potentiation of the production of certain immunoglobulins, but this effect depends on the animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
used. Its use in humans is forbidden by regulatory authorities, due to its toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
. Even for animal research there are currently guidelines
Guideline (medical)
A medical guideline is a document with the aim of guiding decisions and criteria regarding diagnosis, management, and treatment in specific areas of healthcare...
associated with its use, due to its pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
ful reaction and potential for tissue damage. Injections of CFA should be subcutaneous or intraperitoneal, because intradermal injections may cause skin ulceration and necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
; intramuscular injections may lead to temporary or permanent muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
lesion, and intravenous injections may produce pulmonary lipid embolism
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
.
Effects
When administered to mice, in some laboratory experiments Freund's complete adjuvant was said to have prevented juvenile-onset diabetesDiabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
and combined with prepared spleen cells was said to have reversed it. In 2006 these claims were challenged by the findings of several other researchers. Although newspapers have described the 2006 findings as confirming the earlier experiments, in substantial ways they conflict with them. A report from NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
was released on November 23, 2006 in Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....
confirming the participation of spleen cells in reversing end-stage diabetes.
It has also been investigated in an animal model of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
Mechanism
FCA is known to stimulate production of tumor necrosis factorTumor necrosis factors
Tumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...
, which is thought to kill the T-cells responsible for the autoimmune destruction of the pancreatic Beta cells. Still in question is whether the regrowth of functional insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-producing cells occurs due to differentiation and proliferation
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
of existing pancreatic
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
stem cells, or whether the injected spleen cells re-differentiate to an insulin-producing form. Denise Faustman
Denise Faustman
Denise L. Faustman, is a U.S. physician and medical researcher. An Associate Professor of Medicine at Harvard University and Director of the Immunobiology Laboratory at Massachusetts General Hospital, her work specializes in diabetes mellitus type 1 and other autoimmune diseases...
, whose work has been central to developing the protocol, has suggested that both mechanisms may play a role. However, in experiments to verify and examine her work, Suri reported that DNA-based evidence yielded no sign of spleen cell derivatives in pancreatic islet
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
Beta cells analyzed after treatments.
External links
- Recommendations for Use and Alternatives to Freund's Complete Adjuvant. University of IowaUniversity of IowaThe University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees...