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Cytokines

Cytokines

Cytokines are a group of immune-modulating agents (they alter the body’s immune response) that have a similar action to hormones. They’re not classified as hormones because they don’t come from glands. However, they produce a powerful and widespread effect on the body (rather than being restricted to a small or specific area).

Since Covid-19, people have heard of “cytokine storms” and their key role in inflammatory responses, but they also play essential parts in an embryo’s developmental processes. Cytokines include immune-modulating agents such as:

  • Interleukins (ILs).
  • Interferons (IFNs).
  • Tumor necrosing factors (TNF-α).

A variety of cells (including white blood cells) produce cytokines, and they’re often spread around the body. By contrast, hormones production is in discrete glands. Hormones also circulate in small concentrations, and their levels vary by small orders of magnitude of 1 to 10. During trauma or an infection, some cytokine levels will increase by over 1,000 times.

The cytokines that have significant roles in fertility include tumour necrosing factors (TNF-α) and leptin:

  • Raised levels of TNF-α are associated with inflammation, and they can reduce the likelihood of a successful pregnancy. Rather confusingly, they’re also essential for pregnancy, so the concentrations and types of TNF-α involved is crucial.
  • Leptin is made by fat (adipose) tissue and has an important role (along with insulin) in regulating metabolism, appetite and sexual development. Resistance to high levels of leptin is associated with polycystic ovary syndrome (PCOS) and metabolic syndrome. However, low leptin levels can cause another fertility problem; “hypogonadotrophic hypogonadism” (low sex hormone levels that stop ovulation, usually in women with low BMI).

Women with PCOS usually have high levels of several cytokines (including TNF-α, IL-6 and IL-10) in their follicular fluid. Their presence indicates an abnormal immune environment within the follicles of PCOS women, and the high follicular cytokine levels may accelerate PCOS development in the ovaries. i

Abnormal cytokine levels also affect men, and the semen of men with metabolic syndrome have significantly higher cytokine levels, which is linked to lower:

  • Semen volume.
  • Sperm concentration.
  • Sperm count.
  • Sperm motility.
  • Sperm vitality. ii

i Zhang T, Tian F, Huo R, Tang A, Zeng Y, Duan Y-G. Detection of dendritic cells and related cytokines in follicular fluid of patients with polycystic ovary syndrome. Am J Reprod Immunol. 2017;e12717. doi.org/10.1111/aji.12717
ii Leisegang, K., Bouic, P. J. D. and Henkel, R. R. (2016), Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort. Am Jf Reprod Immunol. 76: 155163. doi: 10.1111/aji.12529