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.
Freund's complete 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 by regulatory authorities, 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.
When administered to mice, in some laboratory experiments Freund's complete adjuvant was said to have prevented juvenile-onset diabetes 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.
FCA 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.
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- Qin, HY; Sadelain, MW; Hitchon, C; Lauzon, J; Singh, B (1993), "Complete Freund’s adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice", J. Immunol. 150 (5): 2072–2080, PMID 8436836
- Kodama, S; Kühtreiber, W; Fujimura, S; Dale, EA; Faustman, DL (2003), "Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice", Science 302 (5648): 1223–1227, doi:10.1126/science.1088949, PMID 14615542
- Couzin, J. (2006), "Diabetes Studies Conflict on Power of Spleen Cells", Science 311 (5768): 1694, doi:10.1126/science.311.5768.1694
- Kolata, G. (March 24, 2006), "A Controversial Therapy for Diabetes Is Verified", The New York Times, retrieved May 3, 2010
- New data from NIH lab confirms protocol to reverse type 1 diabetes in mice, BiologyNewsNet, November 2006
- Philip E. Ross, Putting Up with Self, Scientific American, November 12, 2006
- Armentero MT, Levandis G, Nappi G, Bazzini E, Blandini F (2006), "Peripheral inflammation and neuroprotection: systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease", Neurobiol. Dis. 24 (3): 492–505, doi:10.1016/j.nbd.2006.08.016, PMID 17023164.
- Suri, A; Calderon, B; Esparza, TJ; Frederick, K; Bittner, P; Unanue, ER (2006), "Immunological Reversal of Autoimmune Diabetes Without Hematopoietic Replacement of β Cells", Science 311 (5768): 1778–1780, doi:10.1126/science.1123500, PMID 16556846