Freund's adjuvant

Freund's adjuvant is an antigen solution emulsified in mineral oil, used as an immunopotentiator (booster of the immune system).

Forms

The so-called complete form (CFA) is composed of inactivated and dried mycobacteria, usually "Mycobacterium tuberculosis" (the pathogenic agent of tuberculosis).

The so-called incomplete form (IFA) is the same adjuvant, but without the mycobacterial components.

Eponym

It is named after Jules T. Freund (1890-1960), Hungarian-born American immunologist.

Regulation

Freund's adjuvant is effective in stimulating cell-mediated immunity 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, due to its toxicity. Even for animal research there are currently guidelines associated with its use, due to its painful 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.

Effects

When administered to mice, in some laboratory experiments Freund's complete adjuvant was said to have prevented juvenile-onset diabetes [Harvard reference | Surname=Sadelain | Given=M.W., et al. | Title=Prevention of type I diabetes in NOD mice by adjuvant immunotherapy | Journal=Diabetes | Volume=39(5) | Year=1991 | Page=583-589 | URL=http://diabetes.diabetesjournals.org/cgi/content/abstract/39/5/583 ] [Harvard reference | Surname=Qin | Given=H.Y., et al. | Title=Complete Freund’s adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice | Journal=J. Immunol. | Volume=150 | Year=1993 | Page=2072–2080 | URL=http://www.jimmunol.org/cgi/content/abstract/150/5/2072 ] and combined with prepared spleen cells was said to have reversed it. [Harvard reference | Surname=Kodama | Given=S., et al. | Title=Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice | Journal="Science" | Volume=302 | Year=2003 | Page=1223-1227 | URL=http://www.sciencemag.org/cgi/content/abstract/302/5648/1223 ] In 2006 these claims were challenged by the findings of several other researchers. [Harvard reference | Surname=Couzin | Given=J. | Title=Diabetes Studies Conflict on Power of Spleen Cells | Journal=Science | Volume=311 | Year=2006 | Page=1694 | URL=http://www.sciencemag.org/cgi/content/full/311/5768/1694 ] Although newspapers have described the 2006 findings as confirming the earlier experiments, [Harvard reference | Surname=Kolata | Given=G. | Title=A Controversial Therapy for Diabetes Is Verified | Journal=New York Times | Year=2006 March 25 | URL=http://www.nytimes.com/2006/03/24/health/24diabetes.html ] 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. [ [http://www.biologynews.net/archives/2006/11/23/new_data_from_nih_lab_confirms_protocol_to_reverse_type_1_diabetes_in_mice.html New data from NIH lab confirms protocol to reverse type 1 diabetes in mice] , BiologyNewsNet, November 2006] [Philip E. Ross, [http://sciam.com/print_version.cfm?articleID=CE7BB73A-E7F2-99DF-3069CE90D77629FB Putting Up with Self] , Scientific American, November 12, 2006]

It has also been investigated in an animal model of Parkinson's disease.cite journal |author=Armentero MT, Levandis G, Nappi G, Bazzini E, Blandini F |title=Peripheral inflammation and neuroprotection: systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease |journal=Neurobiol. Dis. |volume=24 |issue=3 |pages=492–505 |year=2006 |pmid=17023164 |doi=10.1016/j.nbd.2006.08.016]

Mechanism

The adjuvant is known to stimulate production of tumor necrosis factor, 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. [Harvard reference | Surname=Suri | Given=A., et al. | Title=Immunological Reversal of Autoimmune Diabetes Without Hematopoietic Replacement of β Cells | Journal=Science | Volume=311 | Year=2006 | Page=1778-1780 | URL=http://www.sciencemag.org/cgi/content/abstract/311/5768/1778 ]

ee also

*Adjuvant

External links

* [http://research.uiowa.edu/animal/?get=adjuvant Recommendations for Use and Alternatives to Freund's Complete Adjuvant] . University of Iowa

References