Freund's adjuvant is a solution of

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. ...

emulsified An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although ...

mineral oil Mineral oil is any of various colorless, odorless, light mixtures of higher alkanes from a mineral source, particularly a distillate of petroleum, as distinct from usually edible vegetable oils. The name 'mineral oil' by itself is imprecise, ...

and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant (FCA or CFA) is composed of inactivated and dried

mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...

(usually ''

M. tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

''), whereas the incomplete form (FIA or IFA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after

Jules T. Freund Jules Freund (June 24, 1890 – April 22, 1960) was a Hungarian born American immunologist, most famous for the Freund's adjuvant. According to the ''Journal of Immunology'', "Jules (Julius) Freund studied in Budapest at the Royal Hungari ...

Regulation

Freund's complete adjuvant is effective in stimulating

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 ...

and leads to potentiation of T helper cells that leads to the production of certain

immunoglobulin 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 ...

s and effector T cells. Its use in humans is forbidden by regulatory authorities, due to its

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

. Even for animal research there are currently

guidelines A guideline is a statement by which to determine a course of action. A guideline aims to streamline particular processes according to a set routine or sound practice. Guidelines may be issued by and used by any organization (governmental or pri ...

associated with its use, due to its

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

ful reaction and potential for tissue damage. Injections of FCA should be subcutaneous or intraperitoneal, because intradermal injections may cause

skin ulcer An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin of ...

ation and

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

; intramuscular injections may lead to temporary or permanent

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

lesion, and intravenous injections may produce pulmonary lipid embolism.

Effects

When administered to diabetes prone non-obese diabetic (NOD) mice, Freund's complete adjuvant (FCA) prevented juvenile-onset diabetes. When combined with spleen cells, FCA was said to have reversed diabetes. In 2006, these claims were confirmed that even without spleen cells FCA can restore insulin producing beta cells in pancreas of NOD mice. Although newspapers have described the 2006 findings as confirming the earlier experiments, a report from NIH was released on November 23, 2006 in

Science Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...

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 (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

, or as well used in emulsion with

Myelin oligodendrocyte glycoprotein Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the ''MOG'' gene. It is speculated to serve as a necessary ...

(MOG), a peptide inducing Experimental autoimmune encephalomyelitis (EAE) in animal studies for efficacy testing of

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

treatments.

Mechanism

FCA is known to stimulate production of tumor necrosis factor, which is thought to kill the

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

responsible for the autoimmune destruction of the pancreatic beta cells. Still in question is whether the regrowth of functional

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

-producing cells occurs due to differentiation and proliferation of existing

pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

stem cells, or whether the injected spleen cells re-differentiate to an insulin-producing form.

Denise Faustman Denise Louise Faustman (born 1958) is an American 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 ...

, 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 that spleen cells were needed in

islet beta cells regeneration after the FCA treatment. In pancreatic islets the β-cells regenerate following Freund’s adjuvant treatment. This is related to the induction of

Th17 T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg different ...

cells by adjuvant treatment and these cells produce

Interleukin-22 Interleukin-22 (IL-22) is protein that in humans is encoded by the ''IL22'' gene. Structure IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. IL-22R is expressed o ...

(IL-22).

Pancreatic islets The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...

express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.

References

{{reflist, 30em

External links

Recommendations for Use and Alternatives to Freund's Complete Adjuvant

University of Iowa The University of Iowa (UI, U of I, UIowa, or simply Iowa) is a public university, public research university in Iowa City, Iowa, United States. Founded in 1847, it is the oldest and largest university in the state. The University of Iowa is org ...

Immunology Immune system Animal testing Adjuvants

Regulation

Effects

Mechanism

See also

References

External links