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CC BY-NC-ND 4.0 · Homeopathy 2022; 111(01): 010-021
DOI: 10.1055/s-0041-1732305
Review Article

The Clinical and Biological Effects of Homeopathically Prepared Signaling Molecules: A Scoping Review

Raj Kumar Manchanda 
1   Directorate of AYUSH, Health & Family Welfare Department, Govt of Delhi, New Delhi, India
,
Meeta Gupta
1   Directorate of AYUSH, Health & Family Welfare Department, Govt of Delhi, New Delhi, India
,
Ankit Gupta
1   Directorate of AYUSH, Health & Family Welfare Department, Govt of Delhi, New Delhi, India
,
Robbert van Haselen 
2   International Institute for Integrated Medicine, Kingston, United Kingdom
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Abstract

Background Signaling molecules such as cytokines and interleukins are key mediators for the immune response in responding to internal or external stimuli. Homeopathically prepared signaling molecules have been used therapeutically for about five decades. However, these types of products are not available in many countries and their usage by homoeopaths is also infrequent. The aim of this scoping review is to map the available pre-clinical and clinical data related to the therapeutic use of homeopathically prepared signaling molecules.

Methods We conducted a scoping review of clinical and pre-clinical studies of therapeutically used signaling molecules that have been prepared in accordance with an officially recognized homeopathic pharmacopoeia. Articles in peer-reviewed journals reporting original clinical or pre-clinical research of homeopathically prepared signaling molecules such as interleukins, cytokines, antibodies, growth factors, neuropeptides and hormones, were eligible. Non-English language papers were excluded, unless we were able to obtain an English translation. An appraisal of eligible studies took place by rating the direction of the outcomes on a five-point scale. The quality of the papers was not systematically assessed.

Results Twenty-eight eligible papers, reporting findings for four different manufacturers' products, were identified and reviewed. Seventeen papers reported pre-clinical studies, and 11 reported clinical studies (six experimental, five observational). A wide range of signaling molecules, as well as normal T-cell expressed specific nucleic acids, were used. A majority of the products (21 of 28) contained two or more signaling molecules. The most common clinical indications were psoriasis, vitiligo, rheumatoid arthritis, respiratory allergies, polycystic ovary syndrome, and herpes. The direction of the outcomes was positive in 26 papers and unclear in two papers.

Conclusion This scoping review found that there is a body of evidence on the use of homeopathically prepared signaling molecules. From a homeopathy perspective, these substances appear to have therapeutic potential. Further steps to explore this potential are warranted.

Keywords

cytokines - specific nucleic acids - low dose medicine - signaling molecules

Authors' Contributions

Both R.K. Manchanda and R. van Haselen were involved in the planning, conduct, analysis, and writing of the article. Drs. M. Gupta and A. Gupta were involved in the assessment of the literature papers and in the writing of the article. All authors agree to the contents of the manuscript.


Supplementary Material



Publication History

Received: 23 March 2021

Accepted: 04 June 2021

Article published online:
19 November 2021

© 2021. Faculty of Homeopathy. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 López-Otín C, Kroemer G. Hallmarks of health. Cell 2021; 184: 33-63
    CrossrefPubMedSearch in Google Scholar
  • 2 Bellavite P, Marzotto M, Olioso D, Moratti E, Conforti A. High-dilution effects revisited. 2. Pharmacodynamic mechanisms. Homeopathy 2014; 103: 22-43
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Calabrese EJ, Jonas WB. Homeopathy: clarifying its relationship to hormesis. Hum Exp Toxicol 2010; 29: 531-536
    CrossrefPubMedSearch in Google Scholar
  • 4 Van Wijk R, Wiegant FA. Postconditioning hormesis and the similia principle. Front Biosci (Elite Ed) 2011; 3: 1128-1138
    CrossrefPubMedSearch in Google Scholar
  • 5 Krause CD, Pestka S. Evolution of the Class 2 cytokines and receptors, and discovery of new friends and relatives. Pharmacol Ther 2005; 106: 299-346
    CrossrefPubMedSearch in Google Scholar
  • 6 Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813: 878-888
    CrossrefPubMedSearch in Google Scholar
  • 7 Reilly D, Taylor MA, Beattie NGM. et al. Is evidence for homoeopathy reproducible?. Lancet 1994; 344: 1601-1606
    CrossrefPubMedSearch in Google Scholar
  • 8 WHO. Safety Issues in the Preparation of Homeopathic Medicines. WHO Publications; 2009: 51
    Search in Google Scholar
  • 9 Tricco AC, Lillie E, Zarin W. et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 2018; 169: 467-473
    CrossrefPubMedSearch in Google Scholar
  • 10 Genazzani A, Despini G, Chierchia E, Benedetti C, Prati A. Pharmacological and integrative treatment of stress-induced hypothalamic amenorrhea. In: Genazzani A, Tarlatzis B. eds. Cham: Frontiers in Gynecological Endocrinology: Volume 3: Ovarian Function and Reproduction—From Needs to Possibilities. International Society of Gynecological Endocrinology; 2016: 69-84
    Search in Google Scholar
  • 11 Lotti T. Successful combination treatment for psoriasis with phototherapy and low-dose cytokines: A spontaneous, retrospective observational clinical study. Hautarzt 2015; 66: 849-854
    CrossrefPubMedSearch in Google Scholar
  • 12 Lotti T, Hercogova J, Fabrizi G. Advances in the treatment options for vitiligo: activated low-dose cytokines-based therapy. Review Expert Opin Pharmacother 2015; 16: 2485-2496
    CrossrefPubMedSearch in Google Scholar
  • 13 Luchetti P. Increasing of visual function in patients with retinal atrophy treated with drugs of low dose medicine. Monocentric retrospective observational study. Minerva Oftalmol 2014; 56: 53-61
    PubMedSearch in Google Scholar
  • 14 Rivkina T, Hercogova J, Lotti T. P.N.E.I.: life and death of skin cells. A new paradigm in the treatment of vitiligo: the low dose cytokines therapy. Dermatol Ther (Heidelb) 2016; 29: 134-135
    CrossrefPubMedSearch in Google Scholar
  • 15 Grauwet DJ. Infecciones genitales por VPH tratadas por microinmunoterapia. Rev Méd Homeopat 2011; 4: 103-105
    CrossrefPubMedSearch in Google Scholar
  • 16 Boucinhas JC, De Madeiros Boucinhas ID. Prophylaxie des crises d'asthme bronchique chez l'enfant par l'usage de Poumon histamine 5 CH. Homeopath Fr 1990; 78: 35-39
    PubMedSearch in Google Scholar
  • 17 Nolleveaux MA. Interet de la prescription d'APP (Apis 15 cH, Pulmo-Histaminum 15 cH, Pollantinum 30 cH) dans la rhinite allergique. Observations cliniques en pratique journaliere. Homeopath Fr 1992; 80: 24-33
    PubMedSearch in Google Scholar
  • 18 Barygina V, Becatti M, Lotti T, Moretti S, Taddei N, Fiorillo C. Treatment with low-dose cytokines reduces oxidative-mediated injury in perilesional keratinocytes from vitiligo skin. J Dermatol Sci 2015; 79: 163-170
    CrossrefPubMedSearch in Google Scholar
  • 19 Barygina V, Becatti M, Lotti T, Taddei N, Fiorillo C. Low dose cytokines reduce oxidative stress in primary lesional fibroblasts obtained from psoriatic patients. J Dermatol Sci 2016; 83: 242-244
    CrossrefPubMedSearch in Google Scholar
  • 20 Cardani D, Dusio GF, Luchini P, Sciarabba M, Solimene U, Rumio C. Oral administration of interleukin-10 and anti-IL-1 antibody ameliorates experimental intestinal inflammation. Gastroenterol Res 2013; 6: 124-133
    PubMedSearch in Google Scholar
  • 21 Carello R, Ricottini L, Miranda V. et al. Long-term treatment with low-dose medicine in chronic childhood eczema: a double-blind two-stage randomized control trial. Ital J Pediatr 2017; 43: 78
    CrossrefPubMedSearch in Google Scholar
  • 22 D'Amico L, Ruffini E, Ferracini R, Roato I. Low dose of IL-12 stimulates T cell response in cultures of PBMCs derived from non small cell lung cancer patients. J Cancer Ther 2012; 3: 337-342
    CrossrefPubMedSearch in Google Scholar
  • 23 Fiorito F, Cantiello A, Granato GE. et al. Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma. Comp Immunol Microbiol Infect Dis 2016; 48: 41-47
    CrossrefPubMedSearch in Google Scholar
  • 24 Gariboldi S, Palazzo M, Zanobbio L. et al. Low dose oral administration of cytokines for treatment of allergic asthma. Pulm Pharmacol Ther 2009; 22: 497-510
    CrossrefPubMedSearch in Google Scholar
  • 25 Lotti T, Hercogova J, Wollina U. et al. Vitiligo: successful combination treatment based on oral low dose cytokines and different topical treatments. J Biol Regul Homeost Agents 2015; 29 (Suppl. 01) 53-58
    PubMedSearch in Google Scholar
  • 26 Mancini F, Milardi D, Carfagna P. et al. Low-dose SKA Progesterone and Interleukin-10 modulate the inflammatory pathway in endometriotic cell lines. Int Immunopharmacol 2018; 55: 223-230
    CrossrefPubMedSearch in Google Scholar
  • 27 Martin-Martin LS, Giovannangeli F, Bizzi E. et al. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis. Drug Des Devel Ther 2017; 11: 985-994
    CrossrefPubMedSearch in Google Scholar
  • 28 Radice E, Bellone G, Miranda V. Enhancement of the immunostimulatory functions of ex vivo–generated dendritic cells from early-stage colon cancer patients by consecutive exposure to low doses of sequential-kinetic-activated IL-4 and IL-12. A preliminary study. Transl Oncol 2015; 8: 327-338
    CrossrefPubMedSearch in Google Scholar
  • 29 Radice E, Miranda V, Bellone G. Low-doses of sequential-kinetic-activated interferon-γ enhance the ex vivo cytotoxicity of peripheral blood natural killer cells from patients with early-stage colorectal cancer. A preliminary study. Int Immunopharmacol 2014; 19: 66-73
    CrossrefPubMedSearch in Google Scholar
  • 30 Roberti ML, Ricottini L, Capponi A. et al. Immunomodulating treatment with low dose interleukin-4, interleukin-10 and interleukin-11 in psoriasis vulgaris. J Biol Regul Homeost Agents 2014; 28: 133-139
    PubMedSearch in Google Scholar
  • 31 Tagliacarne SC, Valsecchi C, Benazzo M. et al. Low-dose multicomponent medication modulates humoral and cellular immune response in an ex-vivo study on children subjected to adenoid surgery. Immunol Lett 2018; 203: 95-101
    CrossrefPubMedSearch in Google Scholar
  • 32 Tessaro I, Modina S, Lodde V. et al. Ultra-low doses of follicle stimulating hormone and progesterone attenuate the severity of polycystic ovary syndrome features in a hyperandrogenized mouse model. J Reprod Infertil 2017; 18: 288-297
    PubMedSearch in Google Scholar
  • 33 Tessaro I, Modina SC, Franciosi F. et al. Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome. J Ovarian Res 2015; 8: 64
    CrossrefPubMedSearch in Google Scholar
  • 34 Uberti F, Bardelli C, Morsanuto V, Ghirlanda S, Cochis A, Molinari C. Stimulation of the nonneuronal cholinergic system by highly diluted acetylcholine in keratinocytes. Cells Tissues Organs 2017; 203: 215-230
    CrossrefPubMedSearch in Google Scholar
  • 35 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
    Search in Google Scholar
  • 36 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 2020; 18: 1559325820914092
    Search in Google Scholar
  • 37 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
    CrossrefPubMedSearch in Google Scholar
  • 38 Floris I, Lechner J, Lejeune B. Follow-up of patients with systemic immunological diseases undergoing fatty-degenerative osteolysis of the jawbone surgery and treated with RANTES 27CH. J Biol Regul Homeost Agents 2018; 32: 37-45
    PubMedSearch in Google Scholar
  • 39 Jenaer M, Henry MF, Garcia A, Marichal B. Evaluation of 2LHERP in preventing recurrences of genital herpes. Institut International 3IDI. Br Homeopath J 2000; 89: 174-177
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Lilli NL, Révy D, Robelet S, Lejeune B. Effect of the micro-immunotherapy medicine 2LPARK® on rat primary dopaminergic neurons after 6-OHDA injury: oxidative stress and survival evaluation in an in vitro model of Parkinson's disease. Degener Neurol Neuromuscul Dis 2019; 9: 79-88
    PubMedSearch in Google Scholar
  • 41 Thomas G, Cluzel H, Lafon J, Bruhwyler J, Lajeune B. Efficacy of 2LPAPI®, a micro-immunotherapy drug, in patients with high-risk papillomavirus genital infection. Adv Infect Dis 2016; 6: 7-14
    CrossrefPubMedSearch in Google Scholar
  • 42 Van der Brempt X, Cumps J, Capieaux E. Efficacité clinique du 2L®ALERG, un nouveau traitement de type immunomodulateur par voie sublinguale dans le rhume des foins: une étude en double insu contre placebo. Rev Fr Allergol 2011; 51: 430-436
    CrossrefPubMedSearch in Google Scholar
  • 43 Naidoo P, Pellow J. A randomized placebo-controlled pilot study of Cat saliva 9cH and Histaminum 9cH in cat allergic adults. Homeopathy 2013; 102: 123-129
    Thieme ConnectPubMedSearch in Google Scholar
  • 44 Poitevin B, Davenas E, Benveniste J. In vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica. Br J Clin Pharmacol 1988; 25: 439-444
    CrossrefPubMedSearch in Google Scholar
  • 45 Ruiz-Vega G, Poitevin B, Pérez-Ordaz L. Histamine at high dilution reduces spectral density in delta band in sleeping rats. Homeopathy 2005; 94: 86-91
    Thieme ConnectPubMedSearch in Google Scholar
  • 46 Herr G, Natz A, van Haselen R. The coherency of regulatory requirements for homeopathic medicinal products in the EU and the EAEU. Eur Pharmaceut Law Rev 2019; 3: 58-72
    CrossrefPubMedSearch in Google Scholar
  • 47 Andrianova E, Putilovskiy M. Efficacy and safety of Ergoferon versus oseltamivir: reply to the Letter to the Editor. Int J Infect Dis 2019; 89: 190-192
    CrossrefPubMedSearch in Google Scholar
  • 48 International Journal of Endocrinology. Expression of concern on “Subetta treatment increases adiponectin secretion by mature human adipocytes in vitro”. Int J Endocrinol 2019; 2019: 6595878
    CrossrefPubMedSearch in Google Scholar
  • 49 Petrova NV, Emelyanova AG, Gorbunov EA. et al. Efficacy of novel antibody-based drugs against rhinovirus infection: in vitro and in vivo results. Retracted. Antiviral Res 2017; 142: 185-192
    CrossrefPubMedSearch in Google Scholar
  • 50 Skarnovich MA, Emelyanova AG, Petrova NV. et al. Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice. Antivir Ther 2017; 22: 345-351
    CrossrefPubMedSearch in Google Scholar
  • 51 Tarasov SA, Zarubaev VV, Gorbunov EA, Sergeeva SA, Epstein OI. Activity of ultra-low doses of antibodies to gamma-interferon against lethal influenza A(H1N1)2009 virus infection in mice. Retracted. Antiviral Res 2012; 93: 219-224
    CrossrefPubMedSearch in Google Scholar
  • 52 Petrova NV, Emelyanova AG, Gorbunov EA. et al. Retraction notice to “Efficacy of novel antibody-based drugs against rhinovirus infection: in vitro and in vivo results”. Antiviral Res 2019; 164: 176
    CrossrefPubMedSearch in Google Scholar
  • 53 Skarnovich MA, Emelyanova AG, Petrova NV. et al. Retraction: Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice. Antivir Ther 2019; 24: 235
    CrossrefPubMedSearch in Google Scholar
  • 54 Tarasov SA, Zarubaev VV, Gorbunov EA, Sergeeva SA, Epstein OI. Retraction notice to “Activity of ultra-low doses of antibodies to gamma-interferon against lethal influenza A(H1N1)2009 virus infection in mice”. Antiviral Res 2019; 164: 177
    CrossrefPubMedSearch in Google Scholar
  • 55 ClinicalTrials.gov. Efficacy of 2LALERG (Homeopathic Drug) in allergic rhinitis related to grass pollen (LLB-2016–01). Accessed January 6, 2021 at: https://www.clinicaltrials.gov/ct2/show/results/NCT02690935?term=2LALERG&draw=2&rank=1
    PubMed
  • 56 Belon P, Cumps J, Ennis M. et al. Histamine dilutions modulate basophil activation. Inflamm Res 2004; 53: 181-188
    CrossrefPubMedSearch in Google Scholar
  • 57 Lorenz I, Schneider EM, Stolz P, Brack A, Strube J. Sensitive flow cytometric method to test basophil activation influenced by homeopathic histamine dilutions. Forsch Komplementarmed Klass Naturheilkd 2003; 10: 316-324
    PubMedSearch in Google Scholar
  • 58 Chirumbolo S, Brizzi M, Ortolani R, Vella A, Bellavite P. Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study. Inflamm Res 2009; 58: 755-764
    CrossrefPubMedSearch in Google Scholar
  • 59 Sainte-Laudy J, Belon P. Inhibition of basophil activation by histamine: a sensitive and reproducible model for the study of the biological activity of high dilutions. Homeopathy 2009; 98: 186-197
    Thieme ConnectPubMedSearch in Google Scholar
  • 60 Mathie RT, Roniger H, Van Wassenhoven M. et al. Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study. BMC Med Res Methodol 2012; 12: 49
    CrossrefPubMedSearch in Google Scholar
  • 61 Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 1987; 37: 1097-1102
    CrossrefPubMedSearch in Google Scholar
  • 62 van Zandwijk N, Groen HJM, Postmus PE. et al. Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group. Eur J Cancer 1997; 33: 1759-1766
    CrossrefPubMedSearch in Google Scholar
  • 63 Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 2015; 74: 5-17
    CrossrefPubMedSearch in Google Scholar
  • 64 Bernasconi S. Low dose medicine: theoretical background and scientific evidence. Ital J Pediatr 2018; 44: 23
    CrossrefPubMedSearch in Google Scholar
  • 65 Goldman AW, Burmeister Y, Cesnulevicius K. et al. Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient's autoregulatory capacity?. Front Physiol 2015; 6: 225
    CrossrefPubMedSearch in Google Scholar
  • 66 Hansen MB. Interleukin-6 signaling requires only few IL-6 molecules: relation to physiological concentrations of extracellular IL-6. Immun Inflamm Dis 2020; 8: 170-180
    CrossrefPubMedSearch in Google Scholar