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