IL6 rs1800795 and rs1800796: Inflammation and Immune Response

2 days ago

4 min read

When your body encounters an infection or tissue injury, cells release chemical messages that coordinate the response. Interleukin-6, commonly called IL-6, is one of these signals. It helps regulate immune activity and contributes to fever during infection and inflammation [R]. The IL6 gene provides instructions for producing this protein. Two common regulatory variants—rs1800795 and rs1800796—have been studied for their relationships with IL-6 production, metabolic health, and responses to infection.

You can explore both markers in the free IL6 GeneExplorer report.

Clinician in gloves draws blood from a seated woman in a bright clinic as she watches, calm and focused.

What Does the IL6 Gene Do?

IL-6 is a cytokine, a signaling protein that allows cells to communicate.

Its activities include supporting immune-cell responses and helping coordinate the body’s reaction to inflammation. Its effects also extend into metabolism, linking immune signaling with how tissues handle energy [R, R].

The source and timing of the signal matter. IL-6 released during an acute response does not necessarily have the same implications as persistently elevated signaling.

For related immune pathways, explore our articles on TNF and inflammatory signaling and IL10 and the regulation of inflammation.

IL6 rs1800795: What Did the Original Experiments Find?

Rs1800795, also called −174G>C, lies in the IL6 promoter—a region involved in controlling gene transcription.

In the original study, researchers compared G-containing and C-containing promoter constructs in a laboratory reporter assay. The C-containing promoter showed lower activity.

After stimulation with interleukin-1, activity from the G-containing construct increased approximately 3.6-fold relative to its unstimulated level, while the C-containing construct did not show a significant increase under those conditions [R].

That number describes an experimental response within a cell system. It does not mean GG individuals produce 3.6 times more IL-6 throughout their bodies.

Genotype	Interpretation of the original findings
GG	Two G alleles; the G-containing promoter showed greater activity and responsiveness.
CG	One C and one G allele; this does not establish an exact halfway response.
CC	Two C alleles; the original C-containing promoter showed lower activity under the conditions tested.

These findings established a plausible regulatory role for rs1800795. Later research revealed a more detailed picture.

Why CC Does Not Always Mean Lower IL-6

A 2015 study examined IL-6 production in human fibroblasts, including cells from joint tissue.

Here, the CC genotype was associated with higher IL-6 expression. In contrast, researchers found no association between rs1800795 and IL-6 production in the CD14-positive monocytes they tested [R]. This helps explain apparently conflicting findings. Different cells use different regulatory machinery, and inflammatory stimuli can activate different combinations of signals.

The useful interpretation is therefore specific: rs1800795 has been associated with differences in IL6 regulation, but it is not a universal switch for high or low inflammation.

Rs1800795 and Type 2 Diabetes: A Modest Association

A pooled analysis published in 2006 combined individual participant data from 21 studies involving more than 20,000 people. People with CG or CC, analyzed together, had approximately 9% lower odds of type 2 diabetes than people with GG [R]. The authors described the association as borderline significant and called for confirmation.

Two details matter when reading your genotype:

The estimate applies to CG and CC grouped together. It does not establish extra protection for CC over CG.
A 9% difference in odds is not a nine-percentage-point difference in absolute probability.

For another genetic pathway involved in diabetes susceptibility, read about TCF7L2 rs7903146.

IL6 rs1800796: Immune-Cell Responses to Infection

Rs1800796 is another promoter variant, commonly described as −572G>C or −572C>G.

A 2012 study in Chinese populations investigated this marker using two independent case-control cohorts. Researchers also examined IL-6 production in immune cells stimulated with a protein from Mycobacterium tuberculosis, the bacterium responsible for tuberculosis [R].

Genotype	Finding under the tested immune conditions
GG	Lower stimulated IL-6 production than CC or CG.
CG	Higher stimulated production than GG.
CC	Higher stimulated production than GG; an additional increase over CG was not established.

Across the pooled cohorts—1,878 tuberculosis cases and 1,507 controls—GG was associated with approximately 38% lower tuberculosis odds than CC and CG combined [R].

Why IL-6 Can Rise During Exercise

IL-6 also illustrates why an inflammatory signaling molecule can have different roles under different circumstances. Exercising skeletal muscle releases IL-6. In a small human experiment involving eight healthy men, researchers compared rest, cycling, and infusion of recombinant IL-6. Exercise and IL-6 infusion suppressed the rise in TNF-alpha that otherwise followed an experimental endotoxin challenge [R].

The study supports a role for IL-6 in the body’s response to exercise, including anti-inflammatory effects in that setting. A temporary increase during activity therefore cannot simply be interpreted as harmful inflammation.

For an accessible activity with broader cardiovascular and metabolic benefits, explore our article on the benefits of walking.

What Your IL6 Genotypes Mean for You

These markers can help you explore how inherited variation relates to immune signaling.

Their clearest interpretation comes from asking:

Which cells were studied?
What stimulus was applied?
Was the outcome IL-6 production, a blood measurement, or a disease association?
Which genotypes were compared?

Your results do not measure your current IL-6 concentration or C-reactive protein level. They also cannot establish whether you currently have chronic inflammation.

Explore Your IL6 Results in GeneExplorer

IL6 connects immune defense, inflammatory responses, and metabolism. Its variants show how inherited differences can influence a response while leaving room for the effects of cell type, environment, and current health.

Visit the free IL6 GeneExplorer report to explore rs1800795 and rs1800796. You can analyze your existing raw DNA file in your browser to check which markers are available.