Cytokine dysregulation: one of the causes of Sweet’s syndrome

Updated 29/08/17.

What causes Sweet’s syndrome?

Autoinflammatory conditions such as Sweet’s syndrome are caused by errors in the innate immune system. However, Sweet’s syndrome itself is still a poorly understood condition, but specific causes, i.e. what happens in the body that leads to the symptoms of Sweet’s syndrome, may include hypersensitivity reaction, cytokine dysregulation and genetic susceptibility.

Find out more about the causes for Sweet’s syndrome here.

What are cytokines and cytokine dysregulation?

What are cytokines?

Cytokines are proteins that are produced by cells. They serve as messengers between cells, stimulate the movement of cells towards sites of inflammation, infection and tissue damage, and play a major role in the immune system. The body produces different types of cytokine and these have different functions:

  • Colony stimulating factors (stimulate the production of blood cells).
  • Growth and differentiation factors (function primarily in development).
  • Immunoregulatory and proinflammatory cytokines (interferon, interleukins, and TNF-alpha that function in the immune system).

Their role in the immune system.

The immune system is very complex, and different types of immune cells and proteins do different jobs. Cytokines are amongst those proteins. Cytokines are released by cells into the circulation or directly into tissue. They target specific immune cells and interact with special proteins on these cells (receptors) by binding to them. This interaction causes the immune cell to behave or respond in a particular way.

What is cytokine dysregulation?

Cytokine dysregulation is overproduction or inappropriate production of certain cytokines, and this can result in disease.

Which cytokines are involved in Sweet’s syndrome?

Endogenous granulocyte colony-stimulating factor (G-CSF) and numerous other cytokines have been proven to be involved in Sweet’s syndrome.

Endogenous granulocyte colony-stimulating factor.

  • Endogenous G-CSF is a cytokine that is produced by the body and is associated with an increased white blood cell and neutrophil count, and skin lesions in Sweet’s syndrome patients (Ozlem et al, 2011: 1975).
  • Research shows that patients with active Sweet’s syndrome have higher G-CSF levels than those whose disease is inactive, and G-CSF treatment can trigger Sweet’s syndrome (Ginarte and Toribio, 2011; Kawakami et al, 2004; Paydas, 2013: 87).
  • An increased production of G-CSF caused by cancer cells is a factor in malignancy-associated Sweet’s syndrome (Foster et al, 2005: 145, 148). Research shows that blood cancers such as leukaemia cause an increase in interleukin 1/IL-1 (see below – ‘Other cytokines’) which affects G-CSF levels. G-CSF then recruits neutrophils to the skin via interleukin 6/IL-6 (Yang et al, 2017).

Other cytokines.

  • Granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma, and interleukins (IL-) 1, 2, 3, 6, and 8 can play a role in Sweet’s syndrome (Ginarte and Toribio, 2011; Kumar et al, 2004; Paydas, 2013: 87; Takano et al, 2017).
  • Increased levels of IL-6 have been linked to fever and pain in patients (Ozlem et al, 2011: 1975).
  • IL-6 may play a role in Sweet’s syndrome that has developed secondary to the autoimmune disease systemic lupus erythematosus. This is due to IL-6 and other cytokines being a factor in both conditions (Barton et al, 2011: 5).

References.

Barton, J., Pincus, L., Yazdany, J., Richman, N., McCalmont, T., Gensler, L., Dall’Era, M. and Fye, K. (2011) Association of Sweet’s Syndrome and Systemic Lupus Erythematosus. Case Reports in Rheumatology; Article ID 242681, 6 pages (Hindawi online).

Foster, E., Nguyen, K., Sheikh, R. and Prindiville, T. (2005) Crohn’s disease associated with Sweet’s syndrome and Sjogren’s syndrome treated with Infliximab. Clinical and Developmental Immunology, Jun; 12(2): 145–149 (PDF).

Ginarte, M. and Toribio, J. (2011) Sweet’s Syndrome. IntechOpen (PDF).

Kawakami, T., Ohashi, S., Kawa, Y., Takahama, H., Ito, M., Soma, Y. and Mizoguchi, M. (2004) Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of sweet syndrome and patients with active behcet disease: implication in neutrophil apoptosis dysfunction. Archives of Dermatology, May;140(5):570-4 (online).

Kumar, G., Bernstein, J., Waibel, J. and Baumann, M. (2004) Sweet‘s syndrome associated with sargramostim (granulocyte-macrophage colony stimulating factor) treatment. American Journal of Hematology, Jul;76(3):283-5 (PubMed).

Ozlem, C., Deram. B., Mustafa. S., Koray, T. Cuyan, D. and Ertugrul, T. (2011) Propylthiouracil-induced Anti-neutrophil Cytoplasmic Antibodies and Agranulocytosis together with Granulocyte Colony-stimulating Factor Induced Sweet’s Syndrome in a Patient with Graves’ Disease. Internal Medicine; 50 (18): 1973-1976 (PDF).

Paydas, S. (2013) Sweet’s syndrome: a revisit for hematologists and oncologists. Critical Reviews in Oncology/Hematology, Apr;86(1):85-95 (online).

Takano, Y., Fujino, H., Yachie, A. and Sumimoto, S. (2017) Serum cytokine profile in pediatric Sweet’s syndrome: a case report. Journal of Medical Case Reports, Jul 2;11(1):178 (online).

Yang, M., Kim, J., Kim, G., Song, M., Kim, H., Ko, H., Kim, M. and Kim, B (2017) Neutrophilic Dermatosis of the Palms in Association with Myelodysplastic Syndrome. Annals of Dermatology, Aug; 29(4): 495–497 (online).

© 2012-2017 Sweet’s Syndrome UK

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