Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Abstract Background Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. Methods We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. Results We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. Conclusion This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies

Intrathecal triamcinolone acetonide exerts anti-inflammatory effects on Lewis rat experimental autoimmune neuritis and direct anti-oxidative effects on Schwann cells

Abstract Background Corticosteroids dominate in the treatment of chronic autoimmune neuropathies although long-term use is characterized by devastating side effects. Methods We introduce the intrathecal application of the synthetic steroid triamcinolone (TRIAM) as a novel therapeutic option in experimental autoimmune neuritis in Lewis rats Results After immunization with neuritogenic P2 peptide, we show a dose-dependent therapeutic effect of one intrathecal injection of 0.3 or 0.6 mg/kg TRIAM on clinical and electrophysiological parameters of neuritis with a lower degree of inflammatory infiltrates (T cells and macrophages) and demyelination in the sciatic nerve. In vitro studies in Schwann cell cultures showed an increased expression of IL-1 receptor antagonist and reduced expression of Toll-like receptor 4 after incubation with TRIAM as well as a protective effect of TRIAM against oxidative stress after H2O2 exposure. Conclusion Intrathecal TRIAM application could be a novel immunomodulatory and potentially neuroprotective option for autoimmune neuropathies with a direct effect on Schwann cells

Additional file 2: of Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Figure S2. Capsaicin protects from demyelination: electrophysiological testing in recovery phase and maximum of the disease. (A) In recovery phase of EAN (d 23 p.i.), motor nerve conduction velocity (MNCV) showed a higher nerve conduction velocity in the treated group (50 μg/d). At the maximum of disease, there was no difference between the groups. (B) At disease maximum (d16), the mean compound muscle action potential (CMAP) of the sciatic nerve is more than 50% reduced in control group as an indicator of axonal damage. (C) At disease maximum (d16) F-wave latency was significantly prolonged in control group whereas both treatment groups did not show a prolongation of F-waves. In recovery phase (d23), the group treated with 50 μg/d also showed normal F-wave latencies. (PDF 675 kb

Additional file 1: of Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Figure S1. Experimental design. Experimental overview shows (a) typical disease course in EAN; onset of symptoms between day 8 and 11 p.i.; peak of disease around day 16 p.i.; recovery phase with relief of symptoms around day 23 p.i. (b) Two start points of treatment (late preventive setting starts with day of immunization; early preventive setting imitates a long-term diet and starts 10 days before immunization). (c) Investigation overview at day 16 p.i. and day 23 p.i. (PDF 846 kb

Additional file 3: of Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

Figure S3. Expression of CGRP in the sciatic nerve and regulatory T-lymphocytes in Peyer’s patches did not change. (A) Rats were daily force fed with capsaicin or rapeseed oil from day − 10 p.i. to day 16 p.i. (at expected disease maximum), sciatic nerves were isolated, and RT-PCR of calcitonin gene-related peptide CGRP was performed. Expression of CGRP did not changed significantly in RT-PCR. Mean values and SD were depicted (p = 0.0681, n = 45, n = 15/group, pooled data from three independent experiments). (B) FACS analyses did not show any change of CD4+CD25+FoxP3+ cell population in Peyer’s patches (n = 45, n = 15/group, pooled data from three independent experiments) (PDF 52 kb

Induction of regulatory properties in the intestinal immune system by dimethyl fumarate in lewis rat experimental autoimmune neuritis

$\bf Objective:$ Dimethyl fumarate (DMF) exerts immunomodulatory and neuroprotective effects in the animal model of experimental autoimmune neuritis (EAN) in the Lewis rat. DMF has been shown to modulate gut microbiota in veterinary medicine, however the effects of oral DMF on the gut-associated lymphoid tissue (GALT) remain unknown. $\bf Methods:$ Lewis rats were treated orally twice daily with DMF up to day 10 after immunization with immunogenic P2 peptide. Histological, flow cytometric and RT-PCR analyses of the GALT (intraepithelial layer, lamina propria, and Peyer patches) in duodenum, jejunum, and ileum were performed $\textit {ex vivo}$. Moreover, cell transfer experiments were used to examine the protective effects of GALT regulatory T cells of the Peyer patches. $\bf Results:$ In the upper layers of duodenum, DMF induced a reduction of the toll-like receptor 4 (TLR4) mRNA expression. This was combined by a decrease of the pro-inflammatory lamina propria IFN-$\gamma$ mRNA expression. In the ileum, we detected an immunoregulatory phenotype characterized by an increase of FoxP3 mRNA expression and of the nuclear factor (erythroid-derived-2)- like 2 (Nrf2) downstream molecule heme oxygenase-1 (HO-1) mRNA. Finally, CD4$^{+}$ CD25$^{+}$ regulatory T cells were increased in the Peyer patches. (\textit {In vivo}\), the protective effect of these regulatory cells was verified by cell transfer into recipient EAN rats. $\bf Conclusions:$ Our results identified a novel immunomodulatory effect of DMF through the different regions and layers of the small intestine, which led to an increase of regulatory T cells, exerting a protective role in experimental neuritis

Association of the neonatal Fc receptor promoter variable number of tandem repeat polymorphism with immunoglobulin response in patients with chronic inflammatory demyelinating polyneuropathy

$\textbf {Background and purpose:}$ Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with humoral and cellular autoimmunity causing demyelination of peripheral nerves, commonly treated with intravenous immunoglobulins (IVIg). The neonatal Fc receptor (FcRn), encoded by the $\it FCGRT$ gene, prevents the degradation of immunoglobulin G (IgG) by recycling circulating IgG. A variable number of tandem repeat (VNTR) polymorphism in the promoter region of the $\it FCGRT$ gene is associated with different expression levels of mRNA and protein. Thus, patients with genotypes associated with relatively low FcRn expression may show a poorer treatment response to IVIg due to increased IVIg degradation. $\bf Methods:$ VNTR genotypes were analyzed in 144 patients with CIDP. Patients' clinical data, including neurological scores and treatment data, were collected as part of the Immune-Mediated Neuropathies Biobank registry. $\bf Results:$ Most patients ($\it n$ = 124, 86%) were VNTR 3/3 homozygotes, and 20 patients (14%) were VNTR 2/3 heterozygotes. Both VNTR 3/3 and VNTR 2/3 genotype groups showed no difference in clinical disability and immunoglobulin dosage. However, patients with a VNTR 2 allele were more likely to receive subcutaneous immunoglobulins (SCIg) than patients homozygous for the VNTR 3 allele (25% vs. 9.7%, $\it p$ = 0.02) and were more likely to receive second-line therapy (75% vs. 54%, $\it p$ = 0.05). $\bf Conclusions:$ The VNTR 2/3 genotype is associated with the administration of SCIg, possibly reflecting a greater benefit from SCIg due to more constant immunoglobulin levels without lower IVIg levels between the treatment circles. Also, the greater need for second-line treatment in VNTR 2/3 patients could be an indirect sign of a lower response to immunoglobulins