Prolactin (PRL), the well-known lactogenic hormone, plays a crucial role in immune function given the fact that long term hypoprolactinemia (serum prolactin level below normal) can even lead to death from opportunistic infection. High blood PRL level is known to provide an immunological advantage in many pathological conditions (with some exceptions like autoimmune diseases) and women, because of their higher blood PRL level, get an advantage in this regard. It has been reported that by controlled enhancement of blood PRL level (within the physiological limit and in some cases a little elevated above the normal to induce mild hyperprolactinemia) using dopamine antagonists such immune-stimulatory advantage can led to survival of the patients in many critical conditions. Here it is hypothesized that through controlled augmentation of blood PRL level using dopamine antagonists like domperidone/metoclopramide, which are commonly used drugs for the treatment of nausea and vomiting, both innate and adaptive immunity can be boosted to evade or tone down COVID-19. The hypothesis is strengthened from the fact that at least seven little-understood salient observations in coronavirus patients can apparently be explained by considering the role of enhanced PRL in line with the proposed hypothesis and hence, clinical trials (both therapeutic and prophylactic) on the role of enhanced PRL on the course and outcome of coronavirus patients should be conducted accordingly.
Though it is thought that uncontrolled diabetes and the excessive use of corticosteroids are responsible for COVID-19 associated mucormycosis (CAM), researchers are on the lookout for additional reasons to explain the recent spurt of CAM in India. In the present paper it is argued that melatonin deficiency in COVID-19 plays a major role in CAM. Incidentally, melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-COV-2 downregulates angiotensin-converting enzyme-2, which is the chaperone of the transporter of tryptophan, a key component in the process of uptake of tryptophan. The melatonin deficiency enhances the fungal virulence by facilitating iron acquisition and by promoting morphological transition of the mucor species from the yeast to the virulent hyphal form. Additionally, melatonin deficiency aggravates the suppression of T-cell immunity in the patients receiving steroids. Hence, the restoration of melatonin level should resolve the issues and help in defeating CAM, given the fact that melatonin is an iron chelator, inhibitor of myeloperoxidase, inhibitor of ferroptosis and pyroptosis and calmodulin blocker. Also, by lowering the expression of glucose-regulated protein-78, melatonin can further increase the resistance of diabetic patients to mucormycosis. Hence, clinical trials should be carried out to ascertain how tryptophan supplementation, administration of selective serotonin reuptake inhibitors (to increase serotonin, the precursor of melatonin), and exogenous melatonin help in correcting the melatonin deficiency and eliminating or reducing the propensity of the patients to CAM.
The absence of any drug in the ultra-diluted homeopathic medicines coupled with unfavourable clinical trial results has painted homeopathic remedies as placebos. Different mechanisms have been forwarded to explain the anomalies but with little success. Here it is proposed that homeopathy is a form of protein-based immunotherapy and the immunogenic proteins exist in the microbial lysates, which are present in the homeopathic medicines. The microbial lysates are formed in the homeopathic medicines during their preparation, when microbes from the surrounding environment are unwittingly incorporated into the homeopathic medicines and the microbial cell lysis is induced by alcohol, a component of the drug vehicle (water-alcohol mixture), and augmented by powerful shaking. The drugs in the homeopathic medicines modulate the conformations and, in essence, the immunogenicity of the proteins present in the medicines. The modulated proteins act as immunostimulants and help in boosting and tuning both innate and adaptive immunity. In addition, bystander T cell activation and trained immunity are expected to play important roles in the therapeutic and prophylactic actions of the homeopathic medicines. The importance of dilution in homeopathy vis-à-vis the ‘law of infinitesimals’ can be appreciated by considering the effect of dilution on protein folding and the immunogenicity of proteins. In the case of ultra-diluted homeopathic medicines devoid of any drug molecule, it has been suggested that in the absence of drug-protein interaction, protein-protein interaction leads to the conformational modulation of protein molecules, where allosteric communication and synchronization of vibrating of the protein molecules play key roles. The dictum ‘like cures like’ can be understood by considering the mimicry between the antigens present on the invading pathogen and the antigens present on the proteins in the selected homeopathic medicine. The discrepancies in the clinical trial results of homeopathic medicines arising from the heterogeneities inherent in immunotherapy as well as from a strong placebo response in the clinical trials in some diseases may partly be mitigated by conducting modified clinical trials.
The absence of drugs in ultra-diluted homeopathic medicines and unfavourable clinical trial results portray homeopathic remedies as placebos. Here, it is proposed that homeopathic therapy is a combination of non-specific and antigen-specific mucosal immunotherapy in crude form. The non-specific immunotherapy is mediated by immunomodulatory microbial lysates (disintegration products of microbial cells) present in homeopathic medicines, given that ubiquitous microorganisms from the surrounding environment are unknowingly and unavoidably incorporated into the homeopathic medicines during their preparation and are killed and lysed in alcohol-water vehicle under shaking (‘potentization’) forming microbial lysates whose major ingredients are proteins. As proteins readily interact with a variety of substances, drugs in the homeopathic medicines should bind to the proteins. The drug binding modulates the conformation and effectively, the immunogenicity of the proteins and the latter (designated as drug-modulated proteins) are the agents of antigen-specific immunotherapy. The hypothesis gets some support from the observations that homeopathic medicines elicit immunomodulatory response. Also, the hypothesis without invoking any disputed theory explains the basic tenets of homeopathy and associated controversies like the medicinal properties of ultra-dilutions, where protein-protein interactions via allostery and vibration synchronization bring about conformational modulation of protein molecules in the absence of drugs. As immunotherapy via homeopathic medicines is accidental and accordingly, in rudimentary form, homeopathic treatment (including medicines) cannot be optimal from the standpoint of immunotherapy. Hence, clinical trials in homeopathy may show inconsistent results. However, probing and refining homeopathy from the perspective of immunotherapy may bring forth a novel, simple and affordable immunotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.