• BMB Reports
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• v.54 no.1
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• pp.21-30
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• 2021

Clinical trials have demonstrated that an increased number of effector cells, especially tumor-specific T cells, is positively linked with patients' prognosis. Although the discovery of checkpoint inhibitors (CPIs) has led to encouraging progress in cancer immunotherapy, the lack of either T cells or targets for CPIs is a limitation for patients with poor prognosis. Since interleukin (IL)-2 and IL-7 are cytokines that target many aspects of T-cell responses, they have been used to treat cancers. In this review, we focus on the basic biology of how these cytokines regulate T-cell response and on the clinical trials using the cytokines against cancer. Further, we introduce several recent studies that aim to improve cytokines' biological activities and find the strategy for combination with other therapeutics.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.13-24
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• 2024

Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.192-198
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• 2009

Banhabaikchulcheunma-tang (BBCT), a prescription composed of thirteen herbal mixtures, has been widely used in the treatment of brain disorders in Oriental Medicine. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarction (CI) patients remain unknown yet. The levels of secretory protein of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interlukin (IL)-1b, and IL-6, were significantly increased in lipopolysaccharide (LPS)-stimulated THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from CI patients. However, pretreatment with BBCT significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-a, IL-1b, and IL-6, in THP-1/M cells and PBMCs from CI patients with stimulus. Thus, these data indicate that BBCT may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression on the production of pro-inflammatory cytokines.

• Biomedical Science Letters
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• v.16 no.4
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• pp.287-292
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• 2010

The purpose of this study was to investigate the effects of soybean peptide on lipid peroxidation, antioxidant enzyme and inflammatory cytokines in male high school taekwondo players. The subjects were divided into 2 groups, which were a soybean peptide intake group (S-peptide, n=13) and a placebo intake group (Placebo, n=10). The s-peptide group took 4 g a day of soybean peptide for 4 weeks. Blood samples were taken from the antecubital vein at before taekwondo performance, after 2 and 4 weeks taekwondo performance. The plasma was analyzed for the antioxidant enzyme activity factor, lipid peroxidation and cytokines. As a result, the s-peptide group decreased lipid peroxidation (MDA) and increased the antioxidant enzyme activity factor (TAS and CAT). The plasma concentration of inflammatory cytokines, IL-6 and TNF-${\alpha}$ were significantly decreased in the s-peptide group after 4 weeks and showed significant differences between the groups. These results indicate that the intake of soybean peptide was positively improved on antioxidant enzyme and inflammatory cytokines in taekwondo player.

• Journal of Haehwa Medicine
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• v.9 no.2
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• pp.315-324
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• 2001

To investigate the capacity of anti-inflammatory cytokines and biological response modifiers (BRMs) to induce IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene overexpression from mouse macrophages, we isolated the resident peritoneal macrophages from BALB/c mouse (8 week old) and incubated for 6 h with lipopolysaccaride (LPS) and Moschus moschiferus (MOMS) extracts. Analysis of inflammatory cytokines gene expression was carried out by RT-PCR amplification. Amplified PCR products were electrophoresed on 1.2% agarose gel, and the analysis (Ht) was used to 1D-density program. 1. LPS and MOMS extract treatments resulted in a significant decrease in IL-$1{\beta}$, IL-6, TNF-${\alpha}$ mRNA expression level compared with the LPS treatment. 2. Among four sample of MOMS, Inhibitory effects of MOMS-A and MOMS-D for inflammatory cytokines gene expression were to be fine compared with the MOMS-Band MOMS-C. According to the above data, Because the anti- tumoral and anti-inflammatory response activities of macrophage are known to be dependent on the production of inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) by macrophages, we suggest that evaluations of BRM for the reduction of inflammatory cytokines production by macrophages are important for clinical application.

• Animal cells and systems
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• v.2 no.2
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• pp.153-164
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• 1998

Cytokines regulate proliferation, differentiation and functions of haemotopoietic cells. Each cytokine possesses a variety of activities on various target cells (pleiotropy) and various cytokines have similar and overlapping activities on the same target cells (redundancy). The nature of these cytokine activities predicts unique feature of cytokine receptors, namely, cytokine has multiple receptors, different cytokines share a common receptor, and different cytokine receptors are linked to common signaling pathways. cDNA cloning of genes for cytokine receptors revealed distinct sets of receptor family with different structural features. The cytokine receptor superfamily consists of a largest family, and contains more than twenty cytokine receptor subunits. This receptor has common structural features in both extracellular and intracellular regions without tyrosine kinase domain. Another striking feature of the receptor is to share common subunit of multiple cytokines, which partly explains the redundancy of activities of some cytokines. Recent studies revealed detailed signaling events of the cytokine receptor, the primary activation of JAK and subsequent phosphorylation of tyrosine residues of receptor, and various cellular proteins. Many SH2 containing adapter proteins play an important role in cytokine signals, and this system has similarities with tyrosine kinase receptor signal transduction. STAT may mainly account for cytokine specific functions as suggested by knockout mice studies. It is of importance to note that cytokine activates multiple signaling pathways and the balance and combination of related signaling events may determine the specificity of functions of cytokines.

• IMMUNE NETWORK
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• v.10 no.2
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• pp.55-63
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• 2010

Background: Cordyceps militaris has been used in traditional medicine to treat numerous diseases and has been reported to possess both antitumor and immunomodulatory activities in vitro and in vivo. However, the pharmacological and biochemical mechanisms of Cordyceps militaris extract (CME) on macrophages have not been clearly elucidated. In the present study, we examined how CME induces the production of proinflammatory cytokines, transcription factor, and the expression of co-stimulatory molecules. Methods: We confirmed the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecules. Results: CME dose dependently increased the production of NO and proinflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, and it induced the protein levels of iNOS, COX-2, and proinflammatory cytokines in a concentrationdependent manner, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was also enhanced by CME. Furthermore, the activation of the nuclear transcription factor, NF-${\kappa}B$ in macrophages was stimulated by CME. Conclusion: Based on these observations, CME increased proinflammatory cytokines through the activation of NF-${\kappa}B$, further suggesting that CME may prove useful as an immune-enhancing agent in the treatment of immunological disease.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.1-15
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• 2016

Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants.

• Journal of Oriental Neuropsychiatry
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• v.12 no.1
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• pp.137-149
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• 2001

Cytokines are polypeptides which possess various biological properties affecting. host defense function and response to disease. Inflammatory cytokines, tumor necrosis $factor-{\alpha}$(TNF-${\alpha}$), interleukin(IL)-1 and IL-6 induce inflammation, fever, hypotension and pain when injected into animals or human subject. When glial cell cultures were prepared from neonatal mice or rats, astrocytes were reported to produce these inflammatory cytokines to viral infection, lipopolysaccharide(LPS), or cytokines. The purpose of this study was to investigate the regulatory effect of these cytokines secretion from primary cultures of rat astrocytes. Substance P(SP) can stimulate secretion of TNF-${\alpha}$ from astrocytes stimulated with LPS. Sesim-Tang significantly inhibited the TNF-${\alpha}$ secretion by astrocytes stimulated with SP and LPS. IL-1 has been shown to elevate TNF-${\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-${\alpha}$ secretion from primary astrocytes by Sesim-Tang. Treatment of Sesim-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of TNF-${\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Furthermore Sesim-Tang inhibited the IL-6 secretion by astrocytes stimulated with SP and LPS. The inhibitory effect of inflammatory cytokines by Sesim-Tang, observed in this study, might reflect an antiinflammatory activity and a reduction of various-type pains, fever etc. in the central nervous system.

• CELLMED
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• v.7 no.3
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• pp.15.1-15.6
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• 2017

We analyzed the effects of an Atopic Preventive Drink (APD) on the regulation of Th2 cytokines using RAW 264.7 macrophage cells. In the evaluation of nitric oxide (NO) production in cells, NO production levels were shown to be elevated only in the APD-treated group in a dose-dependent manner. In the lipopolysaccharide (LPS) with APD-treated group, NO production significantly decreased as APD concentration increased. Further, mRNA expression levels and protein concentrations of pro-inflammatory cytokines in cells were determined. Th2 stimulatory cytokine ($IL-1{\beta}$) and Th2 cytokine (IL-6 and IL-10) levels were significantly reduced in the LPS with APD-treated group compared to the only LPS-treated group. mRNA expression levels of inflammatory-related genes (COX-2 and iNOS) were significantly reduced in the LPS with APD-treated group compared to the only LPS-treated group. These results suggest that APD has an anti-atopic effect by reducing mRNA and proteins expressions of Th2 cytokines and inflammatory-related genes.