首页
400-620-6333
Cytokines and Inflammation
Acute?inflammation
The basic function of acute inflammation is to recruit white blood cells from the circulating blood. These cells are mainly neutrophils, followed by monocytes that can differentiate into macrophages or dendritic cells. Inflammatory reaction is accompanied by the degranulation and activation of local mast cell and macrophages, as well as the release of a variety of inflammatory mediators, including bioactive amines (histamine and 5-hydroxytryptamine), cytokines (IL-1 and TNF- α） And chemokines.
The resulting vasodilation and increased Vascular permeability make white blood cells and plasma extravasate to the injured or infected site. Neutrophils then move along the chemotactic gradient created by the components of cytokine and complement pathways, especially C5a. The recruited neutrophils will attempt to disrupt inflammatory factors in order to ultimately resolve and cure inflammation.
Inflammation
If inflammatory factors cannot be removed during acute reactions, or if there are problems with intracellular checkpoints, chronic inflammation can occur. Unresolved chronic inflammation is a core component of a range of chronic diseases, such as autoimmune diseases and neurodegenerative diseases. The pathogenesis of these diseases is related to the continuous production of cytokines1-4.?Compared to acute inflammation, the specific causes and disease progression of chronic inflammation are still unclear.
Detecting the effects of various cytokines is essential for understanding the communication between cells involved in inflammation. A single cytokine can typically act on multiple types of cells and lead to a series of increasingly complex outcomes.
Cytokine imbalance
Bone marrow cells such as dendritic cells, monocytes, and macrophages can secrete pro-inflammatory cytokines, which can activate initial CD4+T cells5. Based on the specific cytokines released, CD4+T cells will further differentiate into different subsets of helper T cells (Th)?4-8.
Cytokines usually have pro-inflammatory or anti-inflammatory effects, and the balance between the two determines the direction of the inflammatory response4. For example, IL-1 β, IL-8 and IFN- γ It is a pro-inflammatory factor that participates in the early response and amplification of inflammatory reactions. Inflammatory cytokines such as IL-4, IL-10, and IL-13 limit the inflammatory response.
Differentiated T cells continue to participate in inflammatory responses and produce their own cytokines, leading to complex interaction networks and various physiological responses. For example, in patients with ulcerative colitis, CD4+T cells that only secrete IL-17 aggregate at the inflamed site of the colon, which is related to a decrease in Th22 cells that only produce IL-229.
Figure 1.?The cytokines involved in the differentiation of specific helper T cells (Th) during the inflammatory process, as well as the cytokines secreted by these cells.
Cytokine therapy
Targeting these inflammatory cytokines is the basis of therapeutic treatment: Krohn's disease was initially treated with anti TNF- α ?Therapy (infliximab - an anti TNF- α ?Chimeric monoclonal antibody (cA2)10. However, designed to neutralize other cytokines such as IFN- γ New drugs such as (fantozumab) and IL-17A (sujinmab) have not been successful and may cause damage to patients with Krohn's disease 11,12. Obviously, cytokines do not operate independently, but are in an activation and inhibition network. Evaluating inflammation by detecting individual cytokines often does not reflect the complexity of inflammation.
Multiple detection of cytokines
To overcome this problem, using multiple detection or multi factor detection is very effective because it can capture multiple different secreted cytokines, allowing us to analyze hundreds of targets simultaneously.
References
1.?Calabrese, F.?et al.IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease.Am. J. Respir.Crit.Care Med.178,?894–901 (2008).
2.?Dinarello, C. a & Kim, S.-H. IL-32, a novel cytokine with a possible role in disease.Ann.Rheum.Dis.65 Suppl 3,?iii61–4 (2006).
3.?Lee, Y. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases.BMB Rep.46,?479-83 (2013).
4.?Neurath, M. F. Cytokines in inflammatory bowel disease.Nat. Rev. Immunol.14,?329-342 (2014).
5.?Kopf, M., Bachmann, M. F. & Marsland, B. J. Averting inflammation by targeting the cytokine environment.Nat. Rev. Drug Discov.9,?703-718 (2010).
6.?Dong, C. & Martinez, G. J. T cells: the usual subsets.Nat. Rev. Immunol.Poster,?(2010).
7.?Kaplan, M. H., Hufford, M. M. & Olson, M. R. The development and in vivo function of T helper 9 cells.Nat. Rev. Immunol.15,?295-307 (2015).
8.?Azizi, G., Yazdani, R. & Mirshafiey, A. Th22 cells in autoimmunity: a review of current knowledge.Eur.Ann.Allergy Clin.Immunol.47,?108-17 (2015).
9.?Leung, J. M.?et al.IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue.Mucosal Immunol.7,?124-133 (2014).
10.?van Dullemen, H. M.?et al.Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2).Gastroenterology?109,?129–135 (1995).
11.?Reinisch, W.?et al.A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn’s disease.Gut?55,?1138–44 (2006).
12.?Balzola, F., Cullen, G., Ho, G. T., Russell, R. K. & Wehkamp, J. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: Unexpected results of a randomised, double-blind placebo-controlled trial.Inflamm.Bowel Dis.Monit.13,?27-28 (2012).
Aladdin：https://www.aladdinsci.com
危险品化学品经营许可证（带存储）