EditorialNatural Immunomodulators 2018

Daniel Ortuño-Sahagún ,1 Ajay K. S. Rawat,2 and Kurt Zänker3

1Instituto de Investigación en Ciencias Biomédicas (IICB), CUCS, Universidad de Guadalajara, Guadalajara, JAL, Mexico2National Botanical Research Institute, Lucknow, Uttar Pradesh, India3Witten/Herdecke University, Witten, Germany

Correspondence should be addressed to Daniel Ortuño-Sahagún; daniel.ortuno.sahagun@gmail.com

Received 25 August 2019; Accepted 28 August 2019; Published 3 November 2019

Copyright © 2019 Daniel Ortuño-Sahagún et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original workis properly cited.

In 2017, the signed editors curated at the state of the art ofimmune science special research results which were per-formed with natural compounds and which approachedimmunomodulation at different molecular levels and fordifferent diseases [1]. The original manuscripts (ms) werepublished in the prestigious Journal of Immunology Research,2017, released by the Hindawi Publishing Corporation. Thisspecial issue was very successful, well taken by the readers,and therefore, there was an urgent demand by the scientificcommunity to get updated latest news in the field of naturalimmunomodulators. Here, in 2019, we present 13 peer-reviewed manuscripts (ms) at the cutting edge of naturalimmunomodulators.

The concept of immunomodulation is, of course, not anew one. The science behind immunomodulation—ingeneral—was carried out with vaccines and by vaccinationand is closely connected, among others, to names likeEdward Jenner, Louis Pasteur, Emil von Behring, and JonasSalk. The biochemical preparations of antigens inducingimmunogenicity and provoking a desired immune defensein the body were a milestone in fighting against infectiousdiseases—this was due to a Western paradigm of medicine.

However, in a unique and holistic world, there is anothertale to give medical and philosophical advice to patients,called holistic medicine, which does not follow a reductionistapproach, likewise to repair—often successfully—symptomsof a diseased body according to a machine model. The morewe are learning that the immune system is navigating thebiopsychosocial well-being and behavior of patients, the

more we try to decipher biological and psychological factorswhich can influence any constituent and function of theimmune system in a specific or nonspecific manner by target-ing the innate and/or the adaptive arm of the immuneresponse.

With these annual special issues, we make known inte-grative knowledge of immunomodulation, which startedout in the past mainly by vaccination, but which will be inthe future multifacetedly shaped by increasingly gatheredknowledge about details of herbs and diet, traditional Chi-nese medicine (TCM), Ayurvedic medicine, psychologicalinterventions, and many other treat-to-target approaches inorder to manipulate the immune system for the benefit ofthe individual, focusing, necessarily in dissecting the cellularand molecular mechanisms subjacent to the immunomodu-latory effects of natural compounds, and for the discoveringof novel promising candidates that can be used in the futureimmunotherapeutic strategies.

One area of recent outstanding interest is the study ofplant-derived immunomodulators [2]. Here, we includedsupporting evidence on the mechanism of action, as immu-nomodulators, of nutraceuticals obtained from Curcumalonga (curcumin), Carthamus tinctorius (safflower), andfrom Alternanthera sessilis.

Twoms by J. R. Macías-Perez et al. addressed the mode ofaction of curcumin with respect to hepatoprotection againstamoebic liver abscess and as cotreatment to reverse livercirrhosis in a hamster model. These results are of importancefor the molecular understanding and treating of common

HindawiJournal of Immunology ResearchVolume 2019, Article ID 4341698, 3 pageshttps://doi.org/10.1155/2019/4341698

liver diseases and illnesses, which have an enormous personaldisease-driven impact and have social and financial influenceon the public health system in countries with low income.The presented results propose that curcumin is a naturalimmunomodulator which can be used as a treat-to-targetcompound.

We accepted the ms by H. Liao et al. because the grouplined out the importance of the different effects of saffloweron protein and mRNA expression of iNOS and IL-1β causedby decoction and injection. The results have to be taken as aclear message that (i) any pharmacological preparation ofbotanicals should be critically scrutinized and (ii) the routingof administration of herbal immunomodulators has to beevaluated in clinical studies.

This continues with the ms by K. Muniandy et al. Thegroup nicely demonstrated that a stem extract of Alter-nanthera sessilis targets the NF-κB pathway and suppressesproinflammatory cytokine production including proinflam-matory mediators like NO and PGE2. NF-κB is oneimportant, if not the key molecule regulating and controllinginfections—but very Janus-faced; it is of high interest thatsuch a herbal stem extract selectively suppresses the proin-flammatory arm of the immune system by targeting NF-κB.

In addition to plant compounds, there is a huge researchon natural compounds able to modulate the immune func-tion. Here, we include an excellent review of the effect ofnatural compounds on NK cell activation. M. Grudzien andA. Rapak describe constituents—from vitamins to polyphe-nols and botanical extracts—which are able to modify theNK activity. This summary might be a scientific proposalfor colleagues to consider one of these constituents as naturalimmunomodulators by using them in different clinicalsettings.

Another area of great interest is the immune response topathogens [3], as in the case of the manuscript by R. Zhenget al. which addressed the cellular T lymphocyte response toBrucella infections and demonstrated that T cell subsets areimbalanced, and the adaptive defense arm of the immunesystem is malfunctioning in patients affected by Brucellosis.Within the follow-up time of the clinical study, the patientsdid not completely recover, so the suggestion by the authorsis to extend the convalescence period in further studies inorder to understand over time increasingly and adequatelythe modified T cell subset answers. Of further attention isthe response to LPS, presented by L. M. Kanevskiy et al.showing results on human NK cells when stimulated withLPS. It was a prevailing opinion that human NK cells donot almost express TLR4 receptors, which are required forLPS stimulation. However, the stimulation response of NKcells, e.g., by producing interferon-gamma, heavily dependson the O-antigen structure of the LPS. Moreover, theinterferon-gamma production between NK cells and macro-phages stimulated by mutant LPS compounds was comparedand they found that NK cells can be significantly shifted tohigher interferon-gamma production as seen under similarexperimental conditions by macrophages.

The immunomodulatory properties of animal substancesand immunotoxicology have attracted increasing attention[4]. Here, a couple of very interesting works deals with these

aspects. The group of J. J. Mora Román et al. reports aboutthe immunomodulating potential of mollusk hemocyanins(KLH) in combination with human vaccine adjuvants in amurine model for oral cancer. The results suggest that theuse of KLH allows a dosage tapering of different adjuvantslike alum, AddaVax, and QS-21. Moreover, the experimentalin vivo results with transplanted MOC-7 cells further suggestthat KLH do exhibit immunomodulation activities by itself.In addition, the ms from the group of G. Mellado-Sánchezet al. is pointing out that immunogenicity against a humandialyzable leucocyte extracts (hDLEs) can be generated bytwo strategies, (i) by chemical conjugation of peptides to acarrier protein as the immunogen and (ii) by using rabbitsto induce antibodies against the peptides in general. Theseapproaches demonstrate in general the impact of developingsurrogate antibodies, which might be directed to any chosentarget, as exemplified with the hDLEs.

Chemical compounds, as artificial sweeteners and vac-cine adjuvants, are also targets of studies on their immuno-modulatory properties. That is the case of the ms by A. Y.Gomez-Arauz et al. that is picking up a tremendous publichealth problem, which is of great worldwide importan-ce—the metabolic syndrome—and therapeutic interventionoptions. The use of artificial sweeteners is very common,but almost nothing is known about their influence on theimmune system. The results clearly show that innocuousconsumption of sucralose has to be critically considered bycaregivers with expertise in metabolic diseases (diabetes, obe-sity) because the expression patterns of monocytes (subpop-ulations) are enigmatically altered.

As mentioned, a ms by A. P. Jiménez-Uribe et al. aboutthe molecular activities on the expression of cytokine levelsinduced by hDLEs, when used as coadjuvant, is publishedin this issue. We considered the results as important, becausethe authors show that the hDLE (Transferon) is a potentimmunomodulator; the spectrum of which—according toimmune modulation—has to be determined in further stud-ies in order to demonstrate in more clinical safety detail.

Finally, several aspects of immunomodulatory therapiesfor clinical development of therapeutic are remarkable andessential to attend [5]. For instance, here, we present someimmunomodulatory aspects related with cancer and withorgan transplant. First, a review by J. Li et al. enlightenedthe evolving roles of macrophages in organ transplantation(OT). OT is a very successful and lifesaving strategy forpatients with end-stage organ failure. It is one of the primeexamples in modern Western medicine for success, and thepublications about OT are multiplexed. Yet, we have selectedthis ms, because the authors nicely discuss the emerging rolesof macrophages on organ transplantation, rejection, andtransplant tolerance in a polytextural content, which is oftenmissing in others, even highly ranked publications. Also, weaccepted the ms by I. Martínez-Reza et al. because any newswith respect to a progress in fighting against triple negativebreast cancer (TNBC) are good news. The group nicely dem-onstrated that calcitriol has antiproliferative effects viamolecular pathways including IL-1β and TNF-alpha andthe receptors of these cytokines. For the future, calcitriolcan be considered as immunomodulator in TNBC.

2 Journal of Immunology Research

We all—the editors and authors with a high reputationin and passion for immunology—are fighting against dif-ferent immune system-driven maladies and, hopefully, willbe able to strengthen sufficiently the immune competenceof immunocompromised patients to regain their healthbenefit. These distributed results are surely a good clinicalbasis and an evidential rationale to consider immunomod-ulators in clinical settings.

Conflicts of Interest

The editors declare that they have no conflicts of interestregarding the publication of this special issue.

Acknowledgments

The editors would like to thank all the authors for submittingtheir manuscripts, having confidence in us regarding thisinitiative, and for their commitment to this proposal. Thishas taken a considerable time, but the result is a timely specialissue including leading-edge research and stimulating dataabout this special issue. We also like to thank the participantreviewers for the rigorous process of peer reviewing. Specialgrateful to Maryam Hazem, who accompanied this processvery patiently.

Daniel Ortuño-SahagúnAjay K. S. Rawat

Kurt Zänker

References

[1] D. Ortuño-Sahagún, K. Zänker, A. K. S. Rawat, S. V. Kaveri,and P. Hegde, “Natural Immunomodulators,” Journal ofImmunology Research, vol. 2017, Article ID 7529408, 2 pages,2017.

[2] I. Jantan, W. Ahmad, and S. N. A. Bukhari, “Plant-derivedimmunomodulators: an insight on their preclinical evaluationand clinical trials,” Frontiers in Plant Science, vol. 6, p. 655,2015.

[3] D. D. Chaplin, “Overview of the immune response,” TheJournal of Allergy and Clinical Immunology, vol. 125, no. 2,pp. S3–23, 2010.

[4] T. Hartung and E. Corsini, “Immunotoxicology: challenges inthe 21st century and in vitro opportunities,” ALTEX, vol. 30,no. 4, pp. 411–426, 2013.

[5] F. R. Brennan, A. Cauvin, J. Tibbitts, and A. Wolfreys, “Opti-mized nonclinical safety assessment strategies supporting clini-cal development of therapeutic monoclonal antibodies targetinginflammatory diseases,” Drug Development Research, vol. 75,no. 3, pp. 115–161, 2014.

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