Cytokines in Disease

 

1ALU HUMAN INTERLEUKIN-6 DOI: 10.2210/pdb1ALU/pdb

 

Cytokine is a general name for Cytokine is a general name for small proteins (~5–20 kDa) that are important in cell signaling. Cytokines have been described as the software that runs the immune system. Cytokines may include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors but generally not hormones or growth factors. One way cytokines differ from hormones is that hormones circulate in nanomolar (10-9 M) concentrations that usually vary by less than one order of magnitude. In contrast, some cytokines (such as IL-6) circulate in picomolar (10-12 M) concentrations that can increase up to 1,000 times during trauma or infection.  Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action). There are both pro-inflammatory cytokines and anti-inflammatory cytokines. (1) In many disease states cytokines are produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines are made by many cell populations, but the predominant producers are helper T cells (Th) and macrophages.

Cytokines in Pain

Proinflammatory cytokines are produced predominantly by activated macrophages and are involved in the up-regulation of inflammatory reactions. There is abundant evidence that certain pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved in the process of pathological pain.(1)

Cytokine release syndrome and Cytokine Storms

Cytokine release syndrome is a form of systemic inflammatory response syndrome that arises as a complication of some diseases or infections, and is also an adverse effect of some monoclonal antibody drugs, as well as adoptive T-cell therapies.(2) Severe cases have been called "cytokine storms" although the the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined.[3]

Cytokines in Autoimmune disease

Interleukin1-α (IL-1α) and IL-1β , along with TNF-α are key inflammatory cytokines in rheumatoid arthritis (RA), TNFα has direct cytotoxic effects on the intestinal mucosa in Crohn's disease and ulcerative colitis but also contributes to the systemic manifestations seen in these diseases. See: Cytokines and Chemokines in Autoimmune Disease: An Overview.

Cytokines in depression

Evidence is accumulating that the levels of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP), are linked to idiopathic major depression. (4)

References

1. Jun-Ming Zhang and Jianxong An. (2007) Cytokines, Inflammation and Pain. Int. Anesthesiol Clin. 45(2): 27-37.

2. Kroschinsky F, Stölzel F, von Bonin S, Beutel G, Kochanek M, Kiehl M, Schellongowski P (April 2017). "New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management". Critical Care. 21 (1): 89.

3. Jennifer R. Tisoncik,a Marcus J. Korth,a Cameron P. Simmons,b Jeremy Farrar,b Thomas R. Martin,c and Michael G. Katz. 2012, Into the Eye of the Cytokine Storm. Microbiol Mol Biol Rev. 2012 Mar; 76(1): 16–32.

4. YektaDowlatiac, NathanHerrmann, Walter Swardfager, Helena Liu, Lauren Sham, Elyse K.Reim, and Krista L.Lanctôt. (2010) Meta-Analysis of Cytokines in Major Depression. Biological Psychiatry Volume 67, Issue 5, 1 March 2010, Pages 446-457.

5. Rai Khalid Farooq Kashif Asghar Shahzina Kanwal Ali Zulqernain. 2016. Role of inflammatory cytokines in depression: Focus on interleukin-1β (Review) https://doi.org/10.3892/br.2016.807 Pages: 15-20.