• 제목/요약/키워드: immune toxicity

검색결과 213건 처리시간 0.022초

Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors

  • Juwhan Choi;Sung Yong Lee
    • IMMUNE NETWORK
    • /
    • 제20권1호
    • /
    • pp.9.1-9.21
    • /
    • 2020
  • Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

Radiation-induced Degradation and Immune Toxicity Reduction of Endosulfan (감마선 조사에 의한 endosulfan의 면역독성 저감)

  • Kim, Hyun-Joo;Kim, Tae-Hoon;Ham, Jun-Sang;Kim, Kee-Hyuk;Jo, Cheo-Run
    • Food Science and Preservation
    • /
    • 제19권3호
    • /
    • pp.451-454
    • /
    • 2012
  • Endosulfan is an organochlorine pesticide that is widely used throughout the world for higher agricultural production. Its extreme toxicity, however, has caused health and environment concerns that have led to an interest in detoxification. In this study, the radiolytic degradation of endosulfan was investigated. Endosulfan in methanol solution (100 ppm) was irradiated at 0, 10, 30, and 50 kGy, and subsequent changes in immune toxicity and degradation of endosulfan were observed. The concentration of endosulfan that was used in this experiment did not affect the cell proliferation. The irradiation of endosulfan decreased the production of NO, indicating a decrease in the immune toxicity of endosulfan by irradiation. The concentration of endosulfan was significantly reduced by irradiation in a dose-dependent manner. The results suggest that gamma irradiation can degrade endosulfan and can reduce its immune toxicity.

Reduction of Immune Toxicity of LPS by Gamma Irradiation (감마선 조사에 의한 LPS의 면역 독성 저감화)

  • Park, Jong-Heum;Sung, Nak-Yun;Byun, Eui-Beak;Song, Du-Sup;Song, Beom-Seok;Kim, Jaekyung;Lee, Ju-Woon;Park, Sang-Hyun;Kim, Jae-Hun;Kang, Geon-Ok;Yoo, Young-Choon
    • Journal of Radiation Industry
    • /
    • 제6권3호
    • /
    • pp.217-221
    • /
    • 2012
  • The purpose of this study is to reduce the immune toxicity of lipopolysaccharide (LPS) by gamma irradiation. LPS was gamma-irradiated at the various doses of 20, 100 and 200 kGy and then evaluated on the immune toxicity through the cell proliferation, nitricoxide production and cytokine release. Cell proliferation significantly decreased in the intact LPS treated groups, whereas gamma-irradiated LPS treated group were not reduced the cell proliferation. Similarly, the production of nitric oxide and cytokine showed the high levels in the intact LPS treated group. However, gamma-irradiated LPS treated group remarkably decreased the production of nitric oxide and cytokine in dose-dependent manner. Therefore, gamma irradiation may effective method to reduce the immune toxicity of LPS.

Environmental Pollution and Gene Expression: Dioxin

  • Kim, Ki-Nam;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
    • /
    • 제1권2호
    • /
    • pp.78-86
    • /
    • 2005
  • Dioxins, especially 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), are ubiquitous environmental contaminants. TCDD is known that it has toxic effects in animals and humans, including chloracne, immune, reproductive and developmental toxicities, carcinogenicity, wasting syndrome and death. TCDD induces a broad spectrum of biological responses, including disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome and cancer. Many researches showed that TCDD induces gene expression of transcriptional factors related cell proliferation, signal transduction, immune system and cell cycle arrest at molecular and cellular levels. These toxic actions of TCDD are usually mediated with AhR (receptor, resulted from cell culture, animal and clinical studies). cDNA microarray can be used as a highly sensitive and informative marker for toxicity. Additionally, microarray analysis of dioxin-toxicity is able to provide an opportunity for the development of candidate bridging biomarkers of dioxin-toxicity. Through microarray technology, it is possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety.

Mutagenicity and Immune Toxicity of Emulsion-type Sausage Cured with Plasma-treated Water

  • Kim, Hyun-Joo;Sung, Nak-Yun;Yong, Hae In;Kim, Hanwool;Lim, Younggap;Ko, Kwang Hyun;Yun, Cheol-Heui;Jo, Cheorun
    • Food Science of Animal Resources
    • /
    • 제36권4호
    • /
    • pp.494-498
    • /
    • 2016
  • Cold plasma has been developed to reduce microbial contamination and to improve safety of food and medical products. In addition, the technology can be used in the manufacture of sausages without addition of nitrite. To be applied in food industry commercially, the new technology should be safe and efficient. However, toxicological test of plasma-treated food is limited. Therefore, the purpose of this study was to determine the mutagenicity and immune toxicity of the meat products cured with plasma-treated water (PTW) as a nitrite source. Emulsion sausages were prepared with no nitrite (control), sodium nitrite (SCS), and PTW (SCP). For a mutagenicity test, the Ames test was performed with the sausage samples. For immune toxicity test, 8-wk-old female Balb/c mice were given free access to the sausages in order to evaluate the tumor necrosis factor (TNF)-α level. As a result, no mutagenicity was detected in the sausages by the Ames test. The serum TNF-α values were less than 10 pg/mL in mice after feeding control and treated samples for 32 d, indicating that no inflammatory response was occurred by feeding the sausages made by PTW. Therefore, the present study opens the possibility of using plasma-treated water as a nitrite source without any toxicity.

The Preventive Effect of Angelica gigas Nakai Extract and Green Coffee BeanExtract on Bone Marrow Toxicity Induced by Benzene (Benzene으로 유도한 골수독성에 대한 참당귀 추출물과 커피 생두 추출물의 예방효과 연구)

  • Eun-Bi Lee;Seo-Kyung Lee;Ye-Jin Hwang;Hyun-Woo Kim;Jae-Seon Kang
    • Journal of Life Science
    • /
    • 제34권9호
    • /
    • pp.620-631
    • /
    • 2024
  • Bone marrow toxicity is a side effect of chemotherapy with anticancer drugs or the exposure to chemicals, such as benzene. When myelotoxicity occurs, the number of white blood cells decreases, which reduces immune functioning and increases the risk of infection or the development of tumors. Angelica gigas Nakai extract (AGNEX) and green coffee bean extract (GCBE) have many effects, such as anti-cancer and antioxidant effects, as well as effects on the immune functioning. In this experiment, the preventive effect of AGNEX and GCBE against benzene-induced bone marrow toxicity was confirmed in Sprague Dawley rats (SD rats) in vivo. Benzene (1 ml/kg mixed with corn oil 1:1) was intraperitoneally administered to SD rats (six weeks, N = 9/group) once a day, and AGNEX (12 mg/kg) and GCBE (6, 12, and 24 mg/kg) were administered orally daily for five weeks. To determine the preventive effect, AGNEX (12 mg/kg) and GCBE (6, 12, and 24 mg/kg) were administered orally before the administration of benzene. Consequently, AGNEX 12 mg/kg and GCBE 12 mg/kg were effective at reducing leukocytes and lymphocytes, specifically granulocyte. Additionally, the treatment also showed protective effects specifically on spleen and liver weight changes and spleen damage. Through this protective effect, AGNEX and GCBE were confirmed to prevent bone marrow toxicity by enhancing the functioning of the immune system.

Dysregulation of Cellular Immune Functions on Gastric Administration to Mixtures of Polyethlene Microplastics and Metallic Lead in Mice (폴리에틸렌 미세플라스틱과 납의 복합노출에 따른 실험동물의 세포면역기능 조절 장애 평가)

  • Gyoungwoo Lee;Changyul Kim
    • Journal of Environmental Health Sciences
    • /
    • 제49권1호
    • /
    • pp.22-29
    • /
    • 2023
  • Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for TH1 cytokines namely, TNF-α and IFN-𝛾 and TH2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased TH1 response with elevated TNF-α and IFN-𝛾 levels and downregulated TH2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to TH1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant TH2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of TH1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to TH1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

Effects of Panax ginseng on Morphine-induced Immune Suppression

  • Lee, Shee-Yong;Kim, Ae-Young;Kim, Young-Ran;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
    • /
    • 제3권3호
    • /
    • pp.177-181
    • /
    • 1995
  • To investigate the possibility of Panax ginseng as a therapeutic agent for the immune suppression, ginseng total saponin (GTS) extracted from korean red ginseng was tested on immune functions from morphine-induced immune suppressed mice. To study how immune functions are affected by morphine and also to test whether GTS can be an useful therapeutic agent for morphine toxicity, several parameters were employed, body weight, immune organ weight, B cell functions, and T cell function. Morphine impaired the development of body weight and immune organ weight such as spleen and thymus. Morphine also depressed a B-cell function, antibody production. T-cell functions studied by type IV hypersensitivity test were most markedly affected by morphine treatment. GTS restored most of morphine-induced immune suppression. GTS restored the morphine-induced decrease in spleen weight to body weight ratio in a dose dependent manner, but not the body weight decrease. Also all of the morphine-induced impairments of B cell functions and cellmediated immunity were fully recovered by GTS. These results suggest that ginseng product could be very helpful for the treatment of immune suppression occurring in morphine abusers.

  • PDF

Effect of Di-(2-ethyl hexyl) Phthalate on Immune Response in Mice (Di-(2-ethyl hexyl) phthalate가 mouse의 면역 반응에 미치는 영향)

  • 임수한;홍사욱;안영근;정규혁
    • Environmental Analysis Health and Toxicology
    • /
    • 제4권1_2호
    • /
    • pp.67-73
    • /
    • 1989
  • Recently pathotoxicological study of lymphoid organs by administration of some phthalate ester in rats, indicated marked effect of architechure of thymus, spleen, and lymphonodes. Dioctyl phthalate (DOP), one of the phthalate ester, caused statistically significant reduction in the weights of various lymphoid organs. This senstivity of the lymphoid organ to phthalate toxicity which could lead to adverse effects on the immune response and also suppression of immune system. Therfore it is possible the presense of di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate ester as well as DOP, in spleen and other organs might have some moderately effect on the function of the immune system, So our present study was proceeded to assess the effect of DEHP on the immunotoxicity in mouse. In the immune response of DEHP administered mice, HA, HY, Arthus reaction and Rosette forming cell were decreased but DTH was increased. Furthermore, in the DEHP plus ethanol group, HA, HY, Arthus reaction and Rosette forming cell were remarkably decreased and elevation of DTH was inhibited.

  • PDF

Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
    • /
    • 제4권4호
    • /
    • pp.267-277
    • /
    • 2008
  • Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.