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 (FCA or CFA) is composed of inactivated and dried mycobacteria (usually M. tuberculosis), 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.
Freund's complete adjuvant is effective in stimulating cell-mediated immunity and leads to potentiation of T helper cells that leads to the production of certain immunoglobulins and effector T cells. 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 FCA 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 diabetes prone 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 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 that spleen cells were needed in pancreatic 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 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). Pancreatic islets express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.
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