Analysis reveals serum levels of 4 chemokines associated with rosacea severity
In this new analysis, the results showed that CCL3, CXCL8, CXCL9 and CXCL10 can be indicators of disease severity.
Researchers shed light on serum indicators that may be associated with disease severity in rosacea patients. While previous research has offered insight into the upregulation of certain chemokines in skin lesions from rosacea patients and in mouse models, the levels of these chemokines have not been widely studied.
In this new analysis of serum levels from 33 patients and 17 healthy controls, results showed that CCL3, CXCL8, CXCL9 and CXCL10 could be indicators of disease severity, which the researchers believe could open the door to new targeted therapies in the future.
“The increase in these circulating serum chemokines in rosacea patients may also provide evidence for the controversial hypothesis that rosacea is not simply a localized skin inflammatory disease, but should be considered a systemic disease,” commented the researchers.
“Rosacea has been widely demonstrated to be closely associated with a wide variety of comorbidities, particularly neurological disorders (Parkinson’s disease, Alzheimer’s disease and migraine) and gastrointestinal disorders (Crohn’s disease, ulcerative colitis and small intestinal bacterial overgrowth) and the gut-brain-skin axis has been postulated to play a key role in rosacea comorbidities,” they added.
A total of 8 chemokines – CCL2, CCL3, CCL20, CXCL1, CXCL8, CXCL9, CXCL10 and CXCL12 – were analyzed in the study. Compared to controls, rosacea patients had elevated levels of CCL3, CXCL8, CXCL9, and CXCL10. Due to the small sample size, the researchers also applied logistic regression to control for age and gender, which confirmed their findings.
Across these 4 chemokines, the researchers tested associations with disease severity, finding that levels of CCL3, CXCL8, and CXCL9 showed positive correlations with the Investigator’s Global Assessment score and levels of CXCL9 and CXCL10 showed positive associations with clinician erythema assessment scores.
“Given that CCL3, CXCL8, CXCL9 and CXCL10 are important mediators of inflammation, it is not surprising to find elevation of these chemokines in other inflammatory diseases,” the group wrote.
They continued: “There are many inflammatory diseases that would be easily confused with rosacea in the clinic such as lupus, acne, atopic dermatitis or even psoriasis. Previous efforts have been made to detect circulating chemokines in these diseases. Specifically, circulating CCL3 has been shown to be elevated in atopic dermatitis, but not in lupus, psoriasis.
Previous research from the same group has shown increased production of CCL3 and macrophage M1 polarization are present in rosacea, which the researchers believe may explain the levels of CCL3 in serum. They also noted that upregulation of CCL3 has been shown to be associated with depression, which has a high prevalence in patients with rosacea.
In another part of the current study, the levels of CCL3, CXCL8, CXCL9 and CXCL10 were explored in a mouse model. These results showed that the corresponding chemokine receptors were all significantly increased in the skin lesions. In human samples, CXCR2 and CXCR3 were found to be greatly increased in people with rosacea. There was no significant difference in the expression of CCR1 or CXCR1 between rosacea patients and controls.
Liu T, Li J, Deng Z, et al. Increased serum levels of CCL3, CXCL8, CXCL9 and CXCL10 in patients with rosacea and their correlation with disease severity. J-Dermatol. Published online March 1, 2022. doi: 10.1111/1346-8138.16329