Special Focus on the Cellular Anti-Inflammatory Effects of Several Micro-Immunotherapy Formulations: Considerations Regarding Intestinal-, Immune-Axis-Related- and Neuronal-Inflammation Contexts

References

• Pahwa R, Goyal A, Jialal I. Chronic Inflammation. In: StatPearls. StatPearls Publishing; 2022.
   Google Scholar
• Wu R-Q, Zhang D-F, Tu E, Chen Q-M, Chen W. The mucosal immune system in the oral cavity—an orchestra of T cell diversity. Int J Oral Sci. 2014;6:125–132. doi:10.1038/ijos.2014.48
   PubMed Web of Science ®Google Scholar
• Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nat Rev Immunol. 2014;14:667–685. doi:10.1038/nri3738
   PubMed Web of Science ®Google Scholar
• Floris I, García-González V, Palomares B, Appel K, Lejeune B. The micro-immunotherapy medicine 2LARTH® reduces inflammation and symptoms of rheumatoid arthritis in vivo. Int J Rheumatol. 2020;2020:1594573. doi:10.1155/2020/1594573
   PubMed Web of Science ®Google Scholar
• Floris I, Chenuet P, Togbe D, Volteau C, Lejeune B. Potential role of the micro-immunotherapy medicine 2LALERG in the treatment of pollen-induced allergic inflammation. Dose-Response Publ Int Hormesis Soc. 2020;18:1559325820914092.
   Web of Science ®Google Scholar
• Jacques C, Chatelais M, Fekir K, et al. The micro-immunotherapy medicine 2LEID exhibits an immunostimulant effect by boosting both innate and adaptive immune responses. Int J Mol Sci. 2022;23:110. doi:10.3390/ijms23010110
   Web of Science ®Google Scholar
• Jacques C, Chatelais M, Fekir K, Brulefert A, Floris I. The unitary micro-immunotherapy medicine interferon-γ (4 CH) displays similar immunostimulatory and immunomodulatory effects than those of biologically active human interferon-γ on various cell types. Int J Mol Sci. 2022;23:2314. doi:10.3390/ijms23042314
   PubMed Web of Science ®Google Scholar
• Decker M-L, Gotta V, Wellmann S, Ritz N. Cytokine profiling in healthy children shows association of age with cytokine concentrations. Sci Rep. 2017;7:17842. doi:10.1038/s41598-017-17865-2
   PubMed Web of Science ®Google Scholar
• Floris I, Rose T, Rojas JA, et al. Pro-inflammatory cytokines at ultra-low dose exert anti-inflammatory effect in vitro, A possible mode of action involving sub-micron particles? Dose-Response Publ Int Hormesis Soc. 2020;18:1559325820961723.
   Web of Science ®Google Scholar
• Floris I, Appel K, Rose T, Lejeune B. 2LARTH®, a micro-immunotherapy medicine, exerts anti-inflammatory effects in vitro and reduces TNF-α and IL-1β secretion. J Inflamm Res. 2018;11:397–405. doi:10.2147/JIR.S174326
   PubMed Web of Science ®Google Scholar
• Jacques C, Floris I, Lejeune B. Ultra-low dose cytokines in rheumatoid arthritis, three birds with one stone as the rationale of the 2LARTH® micro-immunotherapy treatment. Int J Mol Sci. 2021;22:6717. doi:10.3390/ijms22136717
   PubMed Web of Science ®Google Scholar
• Bennett JM, Reeves G, Billman GE, Sturmberg JP. Inflammation-nature’s way to efficiently respond to all types of challenges. Implications for understanding and managing ‘the epidemic’ of chronic diseases. Front Med. 2018;5:316.
   PubMed Web of Science ®Google Scholar
• Jacobson A, Yang D, Vella M, Chiu IM. The intestinal neuro-immune axis, crosstalk between neurons, immune cells, and microbes. Mucosal Immunol. 2021;14:555–565. doi:10.1038/s41385-020-00368-1
   PubMed Web of Science ®Google Scholar
• Cotton JA, Platnich JM, Muruve DA, et al. Interleukin-8 in gastrointestinal inflammation and malignancy, induction and clinical consequences. Int J Interferon Cytokine Mediat Res. 2016;8:13–34.
   Google Scholar
• Kumar S, Shukla R, Ranjan P, Kumar A. Interleukin-10, A compelling therapeutic target in patients with irritable bowel syndrome. Clin Ther. 2017;39:632–643. doi:10.1016/j.clinthera.2017.01.030
   PubMed Web of Science ®Google Scholar
• Tsuge K, Inazumi T, Shimamoto A, Sugimoto Y. Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases. Int Immunol. 2019;31:597–606. doi:10.1093/intimm/dxz021
   PubMed Web of Science ®Google Scholar
• Couper KN, Blount DG, Riley EM. IL-10, the master regulator of immunity to infection. J Immunol. 2008;180:5771–5777. doi:10.4049/jimmunol.180.9.5771
   PubMed Web of Science ®Google Scholar
• Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32:23–63. doi:10.1615/CritRevImmunol.v32.i1.30
   PubMed Web of Science ®Google Scholar
• Li MO, Flavell RA. Contextual regulation of inflammation, a duet by transforming growth factor-β and interleukin-10. Immunity. 2008;28:468–476. doi:10.1016/j.immuni.2008.03.003
   PubMed Web of Science ®Google Scholar
• Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11:633–652. doi:10.1038/nrd3800
   PubMed Web of Science ®Google Scholar
• Richards CD. The enigmatic cytokine oncostatin M and roles in disease. ISRN Inflamm. 2013;2013:e512103. doi:10.1155/2013/512103
   PubMedGoogle Scholar
• Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33:127–148. doi:10.1093/intimm/dxaa078
   PubMed Web of Science ®Google Scholar
• Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295. doi:10.1101/cshperspect.a016295
   PubMed Web of Science ®Google Scholar
• Seyfizadeh N, Seyfizadeh N, Gharibi T, Babaloo Z. Interleukin-13 as an important cytokine, A review on its roles in some human diseases. Acta Microbiol Immunol Hung. 2015;62:341–378. doi:10.1556/030.62.2015.4.2
   PubMed Web of Science ®Google Scholar
• Valkanova V, Ebmeier KP, Allan CLCRP. IL-6 and depression, a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 2013;150:736–744. doi:10.1016/j.jad.2013.06.004
   PubMed Web of Science ®Google Scholar
• Kim Y-K, Suh I-B, Kim H, et al. The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania, effects of psychotropic drugs. Mol Psychiatry. 2002;7:1107–1114. doi:10.1038/sj.mp.4001084
   PubMed Web of Science ®Google Scholar
• Park H-J, Shim H-S, An K, et al. IL-4 Inhibits IL-1 β -induced depressive-like behavior and central neurotransmitter alterations. Mediators Inflamm. 2015;2015:941413. doi:10.1155/2015/941413
   PubMed Web of Science ®Google Scholar
• Singer CA, Figueroa-Masot XA, Batchelor RH, Dorsa DM. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J Neurosci off J Soc Neurosci. 1999;19:2455–2463. doi:10.1523/JNEUROSCI.19-07-02455.1999
   PubMed Web of Science ®Google Scholar
• Gresa-Arribas N, Viéitez C, Dentesano G, et al. Modelling neuroinflammation in vitro, a tool to test the potential neuroprotective effect of anti-inflammatory agents. PLoS One. 2012;7:e45227. doi:10.1371/journal.pone.0045227
   PubMed Web of Science ®Google Scholar
• Kim I-D, Lee J-K. HMGB1-binding heptamer confers anti-inflammatory effects in primary microglia culture. Exp Neurobiol. 2013;22:301–307. doi:10.5607/en.2013.22.4.301
   PubMedGoogle Scholar
• Shu Z, Yang B, Zhao H, et al. Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells. Int Immunopharmacol. 2014;19:275–282. doi:10.1016/j.intimp.2014.01.011
   PubMed Web of Science ®Google Scholar
• Vaux DL. Research methods, Know when your numbers are significant. Nature. 2012;492:180–181. doi:10.1038/492180a
   PubMed Web of Science ®Google Scholar
• Friedrich M, Pohin M, Powrie F. Cytokine networks in the pathophysiology of inflammatory bowel disease. Immunity. 2019;50:992–1006. doi:10.1016/j.immuni.2019.03.017
   PubMed Web of Science ®Google Scholar
• Lin Z, Huang Y, Jiang H, et al. Functional differences and similarities in activated peripheral blood mononuclear cells by lipopolysaccharide or phytohemagglutinin stimulation between human and cynomolgus monkeys. Ann Transl Med. 2021;9:257. doi:10.21037/atm-20-4548
   PubMed Web of Science ®Google Scholar
• Saeedi BJ, Kao DJ, Kitzenberg DA, et al. HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell. 2015;26:2252–2262.
   PubMed Web of Science ®Google Scholar
• Popa C, Netea MG, Van Riel PL, Van Der Meer JW, Stalenhoef AF. The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res. 2007;48:751–762. doi:10.1194/jlr.R600021-JLR200
   PubMed Web of Science ®Google Scholar
• van der Bruggen T, Nijenhuis S, van Raaij E, Verhoef J, Sweder van Asbeck B. Lipopolysaccharide-induced tumor necrosis factor alpha production by human monocytes involves the Raf-1/MEK1-MEK2/ERK1-ERK2 Pathway. Infect Immun. 1999;67:3824–3829. doi:10.1128/IAI.67.8.3824-3829.1999
   PubMed Web of Science ®Google Scholar
• Lu Y, Wahl LM. Oxidative stress augments the production of matrix metalloproteinase-1, cyclooxygenase-2, and prostaglandin E2 through enhancement of NF-κB activity in lipopolysaccharide-activated human primary monocytes. J Immunol. 2005;175:5423–5429. doi:10.4049/jimmunol.175.8.5423
   PubMed Web of Science ®Google Scholar
• Liu X, Yin S, Chen Y, et al. LPS‑induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF‑κB, STAT3 or AP‑1 activation. Mol Med Rep. 2018;17:5484–5491. doi:10.3892/mmr.2018.8542
   PubMed Web of Science ®Google Scholar
• Rana P, Bagewadi H, Banerjee BD, Bhattacharya SK, Mediratta PK. Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in bacillus Calmette-Guerin-induced depression in mice. J Basic Clin Physiol Pharmacol. 2020;31. doi:10.1515/jbcpp-2019-0016
   PubMedGoogle Scholar
• Collett A, Sims E, Walker D, et al. Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption. Pharm Res. 1996;13:216–221. doi:10.1023/A:1016082829111
   PubMed Web of Science ®Google Scholar
• Martínez-Maqueda D, Miralles B, Recio I. HT29 Cell Line. in the Impact of Food Bioactives on Health, in vitro and ex vivo Models. eds. Verhoeckx K. Springer International Publishing; 2015:113–124. doi:10.1007/978-3-319-16104-4_11
   Google Scholar
• Eckmann L, Jung HC, Schürer-Maly C, et al. Differential cytokine expression by human intestinal epithelial cell lines, regulated expression of interleukin 8. Gastroenterology. 1993;105:1689–1697. doi:10.1016/0016-5085(93)91064-O
   PubMed Web of Science ®Google Scholar
• Neels JG, Pandey M, Hotamisligil GS, Samad F. Autoamplification of tumor necrosis factor-α. Am J Pathol. 2006;168:435–444. doi:10.2353/ajpath.2006.050699
   PubMed Web of Science ®Google Scholar
• Andrews C, McLean MH, Durum SK. Cytokine Tuning of Intestinal Epithelial Function. Front Immunol. 2018;9:1270. doi:10.3389/fimmu.2018.01270
   PubMed Web of Science ®Google Scholar
• Kominsky DJ, Campbell EL, Ehrentraut SF, et al. IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia. J Immunol Baltim Md. 2014;192:1267–1276.
   PubMed Web of Science ®Google Scholar
• Lorén V, Cabré E, Ojanguren I, et al. Interleukin-10 enhances the intestinal epithelial barrier in the presence of corticosteroids through p38 MAPK activity in caco-2 monolayers, A possible mechanism for steroid responsiveness in ulcerative colitis. PLoS One. 2015;10:e0130921. doi:10.1371/journal.pone.0130921
   PubMed Web of Science ®Google Scholar
• Zheng L, Kelly CJ, Battista KD, et al. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2. J Immunol Baltim Md. 2017;199:2976–2984.
   PubMed Web of Science ®Google Scholar
• Gitter AH, Bendfeldt K, Schmitz H, et al. Epithelial barrier defects in HT-29/B6 colonic cell monolayers induced by tumor necrosis factor-alpha. Ann N Y Acad Sci. 2000;915:193–203. doi:10.1111/j.1749-6632.2000.tb05242.x
   PubMed Web of Science ®Google Scholar
• Al-Sadi RM, Ma TY. IL-1β causes an increase in intestinal epithelial tight junction permeability. J Immunol Baltim Md. 2007;178:4641–4649.
   PubMed Web of Science ®Google Scholar
• McLean MH, Neurath MF, Durum SK. Targeting interleukins for the treatment of inflammatory bowel disease—what lies beyond anti-TNF therapy? Inflamm Bowel Dis. 2014;20:389–397. doi:10.1097/01.MIB.0000437616.37000.41
   PubMed Web of Science ®Google Scholar
• Ye X, Sun M. AGR2 ameliorates tumor necrosis factor-α-induced epithelial barrier dysfunction via suppression of NF-κB p65-mediated MLCK/p-MLC pathway activation. Int J Mol Med. 2017;39:1206–1214. doi:10.3892/ijmm.2017.2928
   PubMed Web of Science ®Google Scholar
• Maria-Ferreira D, Nascimento AM, Cipriani TR, et al. Rhamnogalacturonan, a chemically-defined polysaccharide, improves intestinal barrier function in DSS-induced colitis in mice and human Caco-2 cells. Sci Rep. 2018;8:12261. doi:10.1038/s41598-018-30526-2
   PubMed Web of Science ®Google Scholar
• Yu H, Huang X, Ma Y, et al. Interleukin-8 regulates endothelial permeability by down-regulation of tight junction but not dependent on integrins induced focal adhesions. Int J Biol Sci. 2013;9:966–979. doi:10.7150/ijbs.6996
   PubMed Web of Science ®Google Scholar
• Mazzon E, Puzzolo D, Caputi AP, Cuzzocrea S. Role of IL-10 in hepatocyte tight junction alteration in mouse model of experimental colitis. Mol Med. 2002;8:353–366. doi:10.1007/BF03402016
   PubMed Web of Science ®Google Scholar
• Kontoyiannis D, Boulougouris G, Manoloukos M, et al. Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn’s-like inflammatory bowel disease. J Exp Med. 2002;196:1563–1574. doi:10.1084/jem.20020281
   PubMed Web of Science ®Google Scholar
• Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol Baltim Md. 2012;188:21–28.
   PubMed Web of Science ®Google Scholar
• Sheibanie AF, Yen JH, Khayrullina T, et al. The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis. J Immunol Baltim Md. 2007;178:8138–8147.
   PubMed Web of Science ®Google Scholar
• Bethea JR, Gillespie GY, Benveniste EN. Interleukin-1β induction of TNF-α gene expression, Involvement of protein kinase C. J Cell Physiol. 1992;152:264–273. doi:10.1002/jcp.1041520207
   PubMed Web of Science ®Google Scholar
• Park Y-G, Kang SK, Noh SH, et al. PGE2 induces IL-1beta gene expression in mouse osteoblasts through a cAMP-PKA signaling pathway. Int Immunopharmacol. 2004;4:779–789.
   PubMed Web of Science ®Google Scholar
• Kusugami K, Fukatsu A, Tanimoto M, et al. Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent. Dig Dis Sci. 1995;40:949–959. doi:10.1007/BF02064182
   PubMed Web of Science ®Google Scholar
• Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006;8:S3. doi:10.1186/ar1917
   PubMed Web of Science ®Google Scholar
• Mizuno T, Zhang G, Takeuchi H, et al. Interferon-γ directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-γ receptor and AMPA GluRl receptor. FASEB J. 2008;22:1797–1806. doi:10.1096/fj.07-099499
   PubMed Web of Science ®Google Scholar
• Yu Z, Cheng G, Wen X, et al. Tumor necrosis factor alpha increases neuronal vulnerability to excitotoxic necrosis by inducing expression of the AMPA-glutamate receptor subunit GluR1 via an acid sphingomyelinase- and NF-kappaB-dependent mechanism. Neurobiol Dis. 2002;11:199–213. doi:10.1006/nbdi.2002.0530
   PubMed Web of Science ®Google Scholar
• Jana M, Dasgupta S, Saha RN, Liu X, Pahan K. Induction of tumor necrosis factor-α (TNF-α) by interleukin-12 p40 monomer and homodimer in microglia and macrophages. J Neurochem. 2003;86:519–528. doi:10.1046/j.1471-4159.2003.01864.x
   PubMed Web of Science ®Google Scholar
• Vanderwall AG, Milligan ED. Cytokines in pain, harnessing endogenous anti-inflammatory signaling for improved pain management. Front Immunol. 2019;10:3009.
   PubMed Web of Science ®Google Scholar
• Treede R-D, Rief W, Barke A, et al. Chronic pain as a symptom or a disease, the IASP classification of chronic pain for the international classification of diseases (ICD-11). PAIN. 2019;160:19–27. doi:10.1097/j.pain.0000000000001384
   PubMed Web of Science ®Google Scholar
• Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity. 2017;46:927–942. doi:10.1016/j.immuni.2017.06.008
   PubMed Web of Science ®Google Scholar
• Scholz J, Woolf CJ. The neuropathic pain triad, neurons, immune cells and glia. Nat Neurosci. 2007;10:1361–1368. doi:10.1038/nn1992
   PubMed Web of Science ®Google Scholar
• Hess A, Roesch J, Saake M, et al. Functional brain imaging reveals rapid blockade of abdominal pain response upon anti-TNF therapy in crohn’s disease. Gastroenterology. 2015;149:864–866. doi:10.1053/j.gastro.2015.05.063
   PubMed Web of Science ®Google Scholar
• Song D, Li Y, Tang D, Huang L, Yuan Y. Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity. Am J Physiol Gastrointest Liver Physiol. 2014;306:G788–795. doi:10.1152/ajpgi.00318.2013
   PubMed Web of Science ®Google Scholar
• Villarán RF, Espinosa-Oliva AM, Sarmiento M, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system, potential risk factor in Parkinson`s disease. J Neurochem. 2010;114:1687–1700. doi:10.1111/j.1471-4159.2010.06879.x
   PubMed Web of Science ®Google Scholar
• Koopman FA, Chavan SS, Miljko S, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016;113:8284–8289. doi:10.1073/pnas.1605635113
   PubMed Web of Science ®Google Scholar
• Walker AK, Kavelaars A, Heijnen CJ, Dantzer R. Neuroinflammation and Comorbidity of Pain and Depression. Pharmacol Rev. 2014;66:80–101. doi:10.1124/pr.113.008144
   PubMed Web of Science ®Google Scholar
• Connor TJ, Song C, Leonard BE, Merali Z, Anisman H. An assessment of the effects of central interleukin-1β, −2, −6, and tumor necrosis factor-α administration on some behavioural, neurochemical, endocrine and immune parameters in the rat. Neuroscience. 1998;84(3):923–933. doi:10.1016/S0306-4522(97)00533-2
   PubMed Web of Science ®Google Scholar