Multiple Cytokines Elevated in Patients with Keloids: Is It an Indication of Auto-Inflammatory Disease?

Abstract

Background Inflammation seems to play a major role in the pathophysiology of keloids. However, the role of cytokines in keloid pathophysiology has not been fully evaluated with only a few cytokines studied. We undertook this study to compare various cytokines in patients with keloids and a control group of patients without keloids nor family history of keloids so as to determine which cytokines are elevated and could thus be critical in keloid formation. Methods This was a cross-sectional study of patients with keloids and a control group of those without. Patients in both groups were matched for age, sex and body mass index. Their plasma was analyzed for both inflammatory and anti-inflammatory cytokines using the Bio-flex Elisa TM method. Comparisons of cytokines means in both groups were done using Student’s t -test. Results A total of 84 participants with 42 participants in each group were followed during the study. Male to female ratio was 1:2. Age ranges were similar with a mean of 29.6 years. A total of 28 cytokines were assayed. Statistically significant differences were noted in 15 of the 28 cytokines assayed with 11 being elevated more in keloid patients with only four in the non-keloid forming group. Among elevated cytokines in keloid patients were granulocyte colony-stimulating factors, granulocyte-monocyte-colony-stimulating factors, interleukins 4, 6 and 13. Conclusion Patients with keloids have significantly higher cytokines compared with non-keloid forming patients. This finding suggests that keloid formation could be influenced by multiple inflammatory cytokines, an indication that the patient’s immune system could play a role in keloid formation akin to auto-inflammatory disease.

The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

“…In addition to the evidence indicating that IL-17-producing Th17 cells stimulate keloid formation, we also found Th2 cells producing IL-4 and IL-13 in the immune infiltrates, which are considered important mediators in the pathogenesis of fibroproliferative diseases such as sclerodermalike cutaneous syndromes (35), abnormal scarring (36) and keloid formation (37). Furthermore, a recent cross-sectional study by Nangole et al (38) showed that IL-4, IL-13 and a variety of other cytokines were significantly elevated in the plasma of keloid patients compared with normal subjects, leading the authors to speculate that the immune system plays a role similar to that of autoinflammatory disease in the formation of keloid. Among the DEGs involved in the IL-13 signaling pathway identified by the KEGG analysis, CXCL8 was recently confirmed to play an important role in keloid scar formation (39,40).…”

“…Furthermore, a recent cross-sectional study by Nangole et al. ( 37 ) showed that IL-4, IL-13 and a variety of other cytokines were significantly elevated in the plasma of keloid patients compared with normal subjects, leading the authors to speculate that the immune system plays a role similar to that of autoinflammatory disease in the formation of keloid. Among the DEGs involved in the IL-13 signaling pathway identified by the KEGG analysis, CXCL8 was recently confirmed to play an important role in keloid scar formation ( 38 , 39 ).…”

Identification and characterization of four immune-related signatures in keloid

“…In conclusion, the immune system plays an indispensable role in keloid development. Additionally, keloid formation is closely related to inflammatory responses, especially inflammation-related factors, such as interleukin 6, transforming growth factor-β, and tumor necrosis factor-α and inflammation-related cells, such as neutrophils, mast cells, and lymphocytes ( 73 ). The inflammatory response is an adaptive response to adverse stimuli.…”

IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation

“…Therefore, identifying signal pathways underlying fibrogenesis of keloid fibroblasts may shed light on novel therapeutic strategies. IL13 , a key driver of progressive fibrosis (11)(12)(13), has been found to be elevated in keloid patients (14). IL13 has also been reported to induce production of anti-apoptotic proteins and directly enhance myofibroblast function.…”

“…IL-13, a key driver of progressive fibrosis ( 11 – 13 ), has been found to be elevated in keloid patients ( 14 ). IL-13 has also been reported to induce production of antiapoptotic proteins and directly enhance myofibroblast function.…”