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Freund's adjuvant - Wikipedia

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<div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+link+.ambox{margin-top:-1px}html body.mediawiki .mw-parser-output .ambox.mbox-small-left{margin:4px 1em 4px 0;overflow:hidden;width:238px;border-collapse:collapse;font-size:88%;line-height:1.25em}.mw-parser-output .ambox-speedy{border-left:10px solid #b32424;background-color:#fee7e6}.mw-parser-output .ambox-delete{border-left:10px solid #b32424}.mw-parser-output .ambox-content{border-left:10px solid #f28500}.mw-parser-output .ambox-style{border-left:10px solid #fc3}.mw-parser-output .ambox-move{border-left:10px solid #9932cc}.mw-parser-output .ambox-protection{border-left:10px solid #a2a9b1}.mw-parser-output .ambox .mbox-text{border:none;padding:0.25em 0.5em;width:100%}.mw-parser-output .ambox .mbox-image{border:none;padding:2px 0 2px 0.5em;text-align:center}.mw-parser-output .ambox .mbox-imageright{border:none;padding:2px 0.5em 2px 0;text-align:center}.mw-parser-output .ambox .mbox-empty-cell{border:none;padding:0;width:1px}.mw-parser-output .ambox .mbox-image-div{width:52px}@media(min-width:720px){.mw-parser-output .ambox{margin:0 10%}}@media print{body.ns-0 .mw-parser-output .ambox{display:none!important}}</style><table class="box-Technical plainlinks metadata ambox ambox-style ambox-technical" role="presentation"><tbody><tr><td class="mbox-image"><div class="mbox-image-div"><span typeof="mw:File"><span><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/f/f2/Edit-clear.svg/40px-Edit-clear.svg.png" decoding="async" width="40" height="40" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/f2/Edit-clear.svg/60px-Edit-clear.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/f2/Edit-clear.svg/80px-Edit-clear.svg.png 2x" data-file-width="48" data-file-height="48" /></span></span></div></td><td class="mbox-text"><div class="mbox-text-span">This article <b>may be too technical for most readers to understand</b>.<span class="hide-when-compact"> Please <a class="external text" href="https://en.wikipedia.org/w/index.php?title=Freund%27s_adjuvant&amp;action=edit">help improve it</a> to <a href="/wiki/Wikipedia:Make_technical_articles_understandable" title="Wikipedia:Make technical articles understandable">make it understandable to non-experts</a>, without removing the technical details.</span> <span class="date-container"><i>(<span class="date">May 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The <b>complete form</b>, Freund's Complete Adjuvant (FCA or CFA) is composed of inactivated and dried <a href="/wiki/Mycobacterium" title="Mycobacterium">mycobacteria</a> (usually <i><a href="/wiki/Mycobacterium_tuberculosis" title="Mycobacterium tuberculosis">M. tuberculosis</a></i>), whereas the <b>incomplete form</b> (FIA or IFA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after <a href="/wiki/Jules_T._Freund" title="Jules T. Freund">Jules T. Freund</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Regulation">Regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Freund%27s_adjuvant&amp;action=edit&amp;section=1" title="Edit section: Regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Freund's complete adjuvant is effective in stimulating <a href="/wiki/Cell-mediated_immunity" title="Cell-mediated immunity">cell-mediated immunity</a> and leads to potentiation of T helper cells that leads to the production of certain <a href="/wiki/Immunoglobulin" class="mw-redirect" title="Immunoglobulin">immunoglobulins</a> and effector T cells. Its use in humans is forbidden by regulatory authorities, due to its <a href="/wiki/Toxicity" title="Toxicity">toxicity</a>. In animal research there are also strict <a href="/wiki/Guideline_(medical)" class="mw-redirect" title="Guideline (medical)">guidelines</a> associated with its use, due to its potential for <a href="/wiki/Pain" title="Pain">pain</a> and tissue damage. Injections of FCA should be subcutaneous or intraperitoneal, because intradermal injections may cause <a href="/wiki/Skin_ulcer" class="mw-redirect" title="Skin ulcer">skin ulceration</a> and <a href="/wiki/Necrosis" title="Necrosis">necrosis</a>; intramuscular injections may lead to temporary or permanent <a href="/wiki/Muscle" title="Muscle">muscle</a> lesion, and intravenous injections may produce pulmonary lipid <a href="/wiki/Embolism" title="Embolism">embolism</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (October 2017)">citation needed</span></a></i>&#93;</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Effects">Effects</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Freund%27s_adjuvant&amp;action=edit&amp;section=2" title="Edit section: Effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>When administered to diabetes prone non-obese diabetic (NOD) mice, Freund's complete adjuvant (FCA) prevented <a href="/wiki/Diabetes_mellitus_type_1" class="mw-redirect" title="Diabetes mellitus type 1">juvenile-onset diabetes</a>.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">&#91;</span>1<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">&#91;</span>2<span class="cite-bracket">&#93;</span></a></sup> When combined with spleen cells, FCA was said to have reversed diabetes.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">&#91;</span>3<span class="cite-bracket">&#93;</span></a></sup> In 2006, these claims were confirmed that even without spleen cells FCA can restore insulin producing beta cells in pancreas of NOD mice.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> Although newspapers have described the 2006 findings as confirming the earlier experiments,<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">&#91;</span>5<span class="cite-bracket">&#93;</span></a></sup> a report from <a href="/wiki/National_Institutes_of_Health" title="National Institutes of Health">NIH</a> was released on November 23, 2006, in <a href="/wiki/Science_(journal)" title="Science (journal)">Science</a> confirming the participation of spleen cells in reversing end-stage diabetes.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">&#91;</span>6<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">&#91;</span>7<span class="cite-bracket">&#93;</span></a></sup> </p><p>It has also been investigated in an animal model of <a href="/wiki/Parkinson%27s_disease" title="Parkinson&#39;s disease">Parkinson's disease</a>,<sup id="cite_ref-pmid17023164_8-0" class="reference"><a href="#cite_note-pmid17023164-8"><span class="cite-bracket">&#91;</span>8<span class="cite-bracket">&#93;</span></a></sup> or as well used in emulsion with <a href="/wiki/Myelin_oligodendrocyte_glycoprotein" title="Myelin oligodendrocyte glycoprotein">Myelin oligodendrocyte glycoprotein</a> (MOG), a peptide inducing <a href="/wiki/Experimental_autoimmune_encephalomyelitis" title="Experimental autoimmune encephalomyelitis">Experimental autoimmune encephalomyelitis</a> (EAE) in animal studies for efficacy testing of <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a> treatments.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">&#91;</span>9<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Mechanism">Mechanism</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Freund%27s_adjuvant&amp;action=edit&amp;section=3" title="Edit section: Mechanism"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>FCA is known to stimulate production of <a href="/wiki/Tumor_necrosis_factors" class="mw-redirect" title="Tumor necrosis factors">tumor necrosis factor</a>, which is thought to kill the <a href="/wiki/T-cells" class="mw-redirect" title="T-cells">T-cells</a> responsible for the <a href="/wiki/Autoimmune" class="mw-redirect" title="Autoimmune">autoimmune</a> destruction of the pancreatic <a href="/wiki/Beta_cells" class="mw-redirect" title="Beta cells">beta cells</a>. Still in question is whether the regrowth of functional <a href="/wiki/Insulin" title="Insulin">insulin</a>-producing cells occurs due to <a href="/wiki/Differentiation_(cellular)" class="mw-redirect" title="Differentiation (cellular)">differentiation</a> and <a href="/wiki/Cell_division" title="Cell division">proliferation</a> of existing <a href="/wiki/Pancreas" title="Pancreas">pancreatic</a> <a href="/wiki/Adult_stem_cells" class="mw-redirect" title="Adult stem cells">stem cells</a>, or whether the injected spleen cells re-differentiate to an insulin-producing form. <a href="/wiki/Denise_Faustman" title="Denise Faustman">Denise Faustman</a>, 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 <a href="/wiki/Pancreatic" class="mw-redirect" title="Pancreatic">pancreatic</a> <a href="/wiki/Islets_of_Langerhans" class="mw-redirect" title="Islets of Langerhans">islet</a> <a href="/wiki/Beta_cells" class="mw-redirect" title="Beta cells">beta cells</a> regeneration after the FCA treatment.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">&#91;</span>10<span class="cite-bracket">&#93;</span></a></sup> In pancreatic islets the β-cells regenerate following Freund's adjuvant treatment.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">&#91;</span>11<span class="cite-bracket">&#93;</span></a></sup> This is related to the induction of <a href="/wiki/Th17" class="mw-redirect" title="Th17">Th17</a> cells by adjuvant treatment and these cells produce <a href="/wiki/Interleukin-22" class="mw-redirect" title="Interleukin-22">Interleukin-22</a> (IL-22). <a href="/wiki/Pancreatic_islets" title="Pancreatic islets">Pancreatic islets</a> express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Freund%27s_adjuvant&amp;action=edit&amp;section=4" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Immunologic_adjuvant" title="Immunologic adjuvant">Immunologic adjuvant</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Freund%27s_adjuvant&amp;action=edit&amp;section=5" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration 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