Cytokines

Cytokines are a group of immune-modulating agents (they alter the body’s immune response) with similar actions to hormones. However, they’re not classed as hormones because they don’t come from discrete glands. A variety of cells (including white blood cells) produce cytokines, and they’re often spread around the body. rather than coming from identifiable glands.

Hormones are generally more stable and circulate in relatively small concentrations, with their levels tending to vary by orders of magnitude of 1 to 10. In contrast, some cytokine levels will increase by over 1,000 times during traumas or infections, and they produce powerful and widespread effects on the body (rather than being restricted to a small or specific area).

Since Covid-19, we’ve all heard of “cytokine storms” and their role in inflammatory responses, but they’re also essential for some embryonic developmental processes. Cytokines include immune-modulating agents like:

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

Cytokines known to have significant roles in fertility include tumour necrosing factors (TNF-α) and leptin

Tumour necrosing factors (TNF-α)

• Inflammation is associated with elevated TNF-α levels, and they reduce the chances of a successful pregnancy
• Low TNF-α levels are also linked to reduced pregnancy success because a certain level of inflammation is essential for pregnancy to proceed. In short, the concentrations and types of TNF-α active in the womb environment is crucial

Leptin

• Leptin is made by fat (adipose) tissue and has an important role (with insulin) in regulating metabolism, appetite and sexual development. Leptin should increase metabolism and reduce appetite, which will regulate weight (and hormone balance)
• High levels of leptin are associated with polycystic ovary syndrome (PCOS) and metabolic syndrome
• Low levels of leptin can cause “hypogonadotrophic hypogonadism” (low sex hormone levels that stop ovulation, usually in women with low BMI or severe low-fat diets)

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, and the high cytokine levels in the follicles may accelerate PCOS development in the ovaries. ⁱ

Cytokines and Male Fertility

Abnormal cytokine levels also affect male fertility, and men with metabolic syndrome have significantly higher cytokine levels in their semen, which is linked to lower:

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