Freund's adjuvant 4406833 225792824 2008-07-15T12:43:50Z 213.170.46.90 /* Mechanism */ '''Freund's adjuvant''' is an [[antigen]] [[solution]] [[emulsification|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 [[Mycobacterium|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), [[Hungary|Hungarian]]-born [[USA|American]] [[immunologist]]. ==Regulation== Freund's adjuvant is effective in stimulating [[cell-mediated immunity]] and may lead to the potentiation of the production of certain [[immunoglobulin]]s, 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 [[guideline (medical)|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 [[ulcer]]ation 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 [[Diabetes mellitus type 1|juvenile-onset diabetes]]<ref>{{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 }}</ref><ref>{{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 }}</ref> and combined with prepared spleen cells was said to have reversed it.<ref>{{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 }}</ref> In 2006 these claims were challenged by the findings of several other researchers.<ref>{{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 }}</ref> Although newspapers have described the 2006 findings as confirming the earlier experiments,<ref>{{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 }}</ref> in substantial ways they conflict with them. A report from [[National Institutes of Health|NIH]] was released on November 23, 2006 in [[Science (journal)|Science]] confirming the participation of spleen cells in reversing end-stage diabetes.<ref>[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</ref><!-- Nov 23rd Science; need ref data for Harvard ref --><ref>Philip E. Ross, [http://sciam.com/print_version.cfm?articleID=CE7BB73A-E7F2-99DF-3069CE90D77629FB Putting Up with Self], Scientific American, November 12, 2006</ref> It has also been investigated in an animal model of [[Parkinson's disease]].<ref name="pmid17023164">{{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}}</ref> ==Mechanism== The adjuvant is known to stimulate production of [[Tumor necrosis factors|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 [[cell division|proliferation]] of existing [[pancreas|pancreatic]] [[adult stem cells|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.<ref>{{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 }}</ref> ==See 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== {{reflist|2}} [[Category:Immunology]] [[Category:Immune system]] [[Category:Animal testing]] [[de:Freund-Adjuvans]] [[pl:Adiuwant Freunda]]