Journal of Inflammatory and Infectious Medicine

Sustained Unresponsiveness in Oral Immunotherapy for Cow's Milk Allergy

Sukyung Kim — 2025-02-13

Short Communication

Sustained Unresponsiveness in Oral Immunotherapy for Cow’s Milk Allergy

Sukyung Kim ^1,†, Minji Kim ^2,†, Jiwon Kim ², Minyoung Jung ³, Ji Young Lee ⁴, Kangmo Ahn ^1,5 and Jihyun Kim ^1,5,*

¹ Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea

² Department of Pediatrics, Chungnam National University Sejong Hospital, Sejong 30099, Korea

³ Department of Pediatrics, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan 49267, Korea

⁴ Department of Pediatrics, Hallym University Chuncheon Sacred Heart Hospital, Hallym University School of Medicine, Chuncheon 24253, Korea

⁵ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Seoul 06355, Korea

* Correspondence: jhlovechild@gmail.com; Tel.: +82-2-3410-1035; Fax: +82-2-3410-0043

^† These authors contributed equally to this work.

Received: 8 August 2024; Revised: 16 October 2024; Accepted: 22 November 2024; Published: 13 February 2025

Abstract: Background: We aimed to investigate the efficacy and safety of home-based oral immunotherapy (OIT) in children with cow’s milk (CM) allergy (CMA) and to examine whether sustained unresponsiveness (SU) could be achieved after cessation of OIT. Methods: Children with CMA, aged 3–10 years, were enrolled in the OIT (n = 8) and the control (n = 8) groups. Patients increased the dose of heated milk daily at home during the build-up phase. During the maintenance phase, 100 mL of unheated milk (UM) (3.0 g of CM proteins) was administered daily to the patients for 12 months. Oral food challenge (OFC) tests were performed with a total dose of 200 mL of UM after the build-up phase and four weeks after cessation of CM following the maintenance phase. Results: All patients in the OIT group achieved desensitization after completion of the build-up phase. After 12 months of the maintenance phase and four weeks of the CM restriction period, OFC was performed in six patients in the OIT group. Among them, five (83.3%) patients obtained SU, while none of the patients in the control group achieved tolerance (p = 0.003). During OIT, adverse reactions were reported in seven (87.5%) patients. Anaphylaxis occurred in three (37.5%) patients in the OIT group and in four (50.0%) patients in the control group (p = 1.000). There were no serious adverse or life-threatening events during OIT. Conclusions: Home-based milk OIT is an effective and safe treatment method for SU and desensitization to CMA.

Proinflammatory Effects of Obesity in the Progression of Triple Negative Breast Cancer

Deok-Soo Son — 2025-02-14

Article

Proinflammatory Effects of Obesity in the Progression of Triple Negative Breast Cancer

Deok-Soo Son ¹^,*, Rosa Mistica C. Ignacio ¹, Jubin Son ², Eun-Sook Lee ³ and Samuel E. Adunyah ¹

¹ Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA

² Neuroscience Program, College of Arts and Sciences, The University of Tennessee, Knoxville, TN 37996, USA

³ Department of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL 32301, USA

* Correspondence: dson@mmc.edu

Received: 21 August 2024; Revised: 28 October 2024; Accepted: 2 December 2024; Published: 14 February 2025

Abstract: Obesity induces chronic inflammation and is associated with one-fifth of cancer deaths. Triple negative breast cancer (TNBC) has a higher death rate and increased proinflammatory chemokines compared to other breast cancer subtypes. Obesity leads to reduced overall survival in patients with TNBC. Here, we investigated if obesity-induced inflammation is involved in the progression of TNBC using cell line and animal models. Adipocyte-conditioned media (CM) increased cell viability, migration, and proinflammatory chemokines in mouse PY8119 TNBC cells, which reflect well human mesenchymal-like TNBC cells, compared to preadipocyte-CM. The ob/ob mice enhanced the progression of PY8119 cells by increasing the intensity of bioluminescence imaging, tumor volume and weight, and proinflammatory chemokines, compared to the wild-type mice. Furthermore, the immune contexture showed the higher levels of macrophage and CD4 cells in tumors of obese mice. Taken together, obesity may accelerate the progression of TNBC, revealing increased proinflammatory chemokines and altered immune contexture in the tumor microenvironment.

Natural Plant Extracts as Novel Antiviral Candidates: Citrus extracts

Mijeong Choi — 2025-02-18

Article

Natural Plant Extracts as Novel Antiviral Candidates: Citrus extracts

Mijeong Choi ^1,†, Jihyeong Hwang ^2,†, Kwango Han ¹, Hyunjik Noh ¹, Byeongju Kang ¹, Taehwa Jeong ¹, Gyumin Choi ¹, Haekyoung Lee ¹, Yuri Kim ¹, Hanbong Ryu ¹, Sinae Kim ², Heejun Kim ³, and Saerok Shim ^2,*

¹ Biomedical Engineering Research Institute, 32 Dongguk-ro, Goyang-si 10326, Republic of Korea

² The Institute of YbdY Biotechnology, 83, Gasan digital 1-ro, Geumcheon-gu, Seoul 08589, Republic of Korea

³ The Institute of Kulf, 7, Sareung-ro 70 beon-gil, Namyangju-si, Gyeonggi-do 12231, Republic of Korea

* Correspondence: kon316@naver.com; Tel.: +82-2-457-0868; Fax: +82-2-2030-7788

† These authors have contributed equally to this work.

Received: 20 November 2024; Revised: 26 December 2024; Accepted: 12 February 2025; Published: 18 February 2025

Abstract: Medicinal plants are the natural and main source of therapeutic drugs today. The biological activity of several plants has been performed, but many remain to be evaluated. Meanwhile, most biological studies on plants used in traditional medicine concern their antiviral and anti-inflammatory activity. In this study, two sets of plant extracts were studied for their biological activities. Various plant extracts, including Citrus peels, were evaluated for their antiviral activity. Among them, in the first set, three herbs were tested individually, and the five mixtures in the second set were composed of various traditional Korean herb extracts in several proportions. Through appropriate combinations of traditional Korean herbs, the antiviral activity was improved than single herb extracts.

Cytokines in Immune Response and Disorders: Cytokines and Soluble Inhibitors

Soohyun Kim — 2025-03-04

Review

Cytokines in Immune Response and Disorders: Cytokines and Soluble Inhibitors

Soohyun Kim ^1,2,*

¹Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University,
Seoul 05029, Republic of Korea

²College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea

* Correspondence: soohyun@konkuk.ac.kr; Tel.: +82-2-457-0868; Fax: +82-2-2030-7788

Received: 6 October 2024; Revised: 20 January 2025; Accepted: 27 February 2025; Published: 4 March 2025

Abstract: Over a long period of time, animals have built defense mechanisms to block external intruders through a complex evolutionary process. The structure created at the center is called the immune system. In animals with a vascular system, immune cells circulating in the blood perform most of the role. Cytokines are substances that direct immune function and are not only produced by immune cells but also secreted by non-immune cells, contributing to the proliferation and differentiation of blood cells. Most blood cells are red blood cells that supply oxygen in the body, and a small number of white blood cells (WBC) perform immune functions. Even under normal circumstances, mammalian WBC are produced in the bone marrow, differentiate into various immune cells, and proliferate under the stimulation of cytokines. However, when infected with external pathogens, viruses, bacteria, fungi, and parasites, cytokines are produced exponentially and temporarily induce proliferation and differentiation of immune cells defending the host from pathogens. Once all pathogens are destroyed by immune cells, excessive cytokine activity is downregulated by soluble antagonists, such as cytokine binding proteins and ligands, but which have receptor antagonist properties. In this review, we will discuss the roles of cytokines, which are immune enhancers, and soluble cytokine binding proteins, which are immunosuppressants, and various autoimmune diseases that arf44ise from immune imbalance.

cKit Ligand (Stem Cell Factor)-Induced Immune Response via an Alternative Receptor in Human Cells

Jihyung Hwang — 2025-03-10

Article

cKit Ligand (Stem Cell Factor)-Induced Immune Response via an Alternative Receptor in Human Cells

Jihyung Hwang ^1,^†, Angela Reinert ^2,^†, Arthur Stem ², Saerok Shim ¹, Sinae Kim ¹, HeeJoon Kim ³, Myungdal Yoon ³, Seungheon Lee ³, Donghwan Song ³, Hyun Yoo ¹, Sunyoung Han ⁴, Mijeong Choi ⁵, Jared M. Brown ^2,*, and Soohyun Kim ^1,3,*

¹Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University,
Seoul 05029, Republic of Korea

²Department of Pharmaceutical Sciences, Colorado Center for Nanomedicine and Nanosafety, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

³College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea

⁴College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University,
Jinju 52828, Republic of Korea

⁵Biomedical Engineering Research Institute, 32 Dongguk-ro, Goyang-si 10326, Republic of Korea

* Correspondence: jared.brown@cuanschutz.edu (J.M.B.); soohyun@konkuk.ac.kr (S.K.);
Tel.: +82-2-457-0868 (SK); Fax: +82-2-2030-7788 (SK)

† These authors contributed equally to this work.

Received: 9 July 2024; Revised: 7 January 2025; Accepted: 3 March 2025; Published: 10 March 2025

Abstract: cKit (also known as CD117) is known for stem cell factor (SCF) receptor and it is involved in bone marrow hematopoietic stem cell (HSC) proliferation as well as mast cell growth. We have cloned the cDNA of cKit ligand (cKit-L; also known as SCF) from human keratinocyte HaCaT cells. Recombinant HaCaT cKit-L protein was produced and characterized whether it is active on HMC-1 cell expressing very high level of cKit transcript. Interestingly, HMC-1 cells did not respond to its ligand HaCaT cKit-L, whereas the same recombinant HaCaT cKit-L induced inflammatory chemokine interleukin 8 (IL-8) in human THP-1 monocyte cells that do not express cKit (also known as CD117). We wonder if HMC-1 is defective in the production of inflammatory molecules. Nevertheless, HMC-1 cells produce significant amounts of human IL-8 in response to IL-1a and IL-33. Commercial cKit-L was used to confirm these results, and the activity of commercial cKit-L was very similar to that of HaCaT cKit-L. These data suggest that the known cKit-L receptor cKit is required for cKit-L activity but is not sufficient to complete the immunological activity of cKit-L. It is possible that alternative cKit-L receptors exist that are responsible for inducing IL-8 in human and mouse immune cells.

Antiviral Activity of Gallus Recombinant Interferon α3

Myungdal Yoon — 2025-03-12

Article

Antiviral Activity of Gallus Recombinant Interferon α3

Myungdal Yoon ¹, Seungheon Lee ¹, Donghwan Song ¹, Jihyung Hwang ², HeeJoon Kim ¹, Hyun Yoo ², Mijeong Choi ^2,3, and Sinae Kim ⁴^,*

¹College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea

²Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University,
Seoul 05029, Republic of Korea

³Biomedical Engineering Research Institute, 32 Dongguk-ro, Goyang-si 10326, Republic of Korea

⁴The Institute of YbdY biotechnology, 83, Gasan digital 1-ro, Geumcheon-gu, Seoul 08589, Republic of Korea

* Correspondence: seconeco@naver.com; Tel.: +82-2-457-0868; Fax: +82-2-2030-7788

Received: 10 September 2024; Revised: 24 January 2025; Accepted: 10 March 2025; Published: 12 March 2025

Abstract: Interferons (IFNs) were first discovered in 1957 in a nutrient fluid from chick chorioallantois membranes, where it was observed that administration of virus stimulated interferon production in many animals, tissues, and cells, within a short time. They are classified into type 1, type 2, and IFN-like cytokines, with type 1 IFN classified into IFNα, IFNβ, IFNε, IFNκ, IFNω, IFNδ, and IFNτ. Clinical tests for recombinant human IFNs and bovine IFNτ have been conducted since 1981. Although infections of Highly Pathogenic Avian Influenza Virus (HPAI) have continued to cause high economic losses in poultry industry causing many deaths of poultry, few molecular experiments based on gallus (ga) IFNs have been reported since 1994 and clinical trials to test their use are limited. Here, we examined the activities of newly produced three recombinant gaIFNα3s on different species of cells. The recombinant gaIFNα3s showed significant antiviral activity in Gallus embryo fibroblast (GEF) cells, showing good potential to prevent the cytopathic effect of vesicular stomatitis virus (VSV). However, they failed to protect Wistar Institute Susan Hayflick (WISH) cells, Madin-Darby bovine kidney epithelial (MDBK) cells, and Madin-Darby canine epithelial-like (MDCK) cells. This study demonstrated the impact of species specificity on the antiviral activity of gaIFNα3 and the effect of location of fusion protein.