RESUMO
BACKGROUND AND AIMS: IL-1 and IL-18 play important roles in intestine barrier integrity maintenance and inflammatory response. However, their net effects on the risk of IBD are still inconclusive. Here, we used Mendelian randomization (MR) approaches to investigate the causal associations of IL-18 and IL-1Ra (receptor antagonist) on the risks of IBD and subtypes. METHODS: For IL-18, both three-sample and two-sample MR approaches were used for the causal inferences. In three-sample MR, three single nucleotide polymorphisms (SNPs) and the effect values were extracted from two quantitative trait loci (pQTL) datasets with non-overlapping populations. In two-sample MR, we extracted genetic instruments information from the same larger pQTL dataset. For IL-1Ra, we applied the two-sample MR method with summary-statistics from the larger pQTL dataset. Summary-level results of three large IBD/CD/UC genome-wide association studies in European ancestry were employed. Inverse-variance weighted method, various sensitivity analyses and meta-analysis were performed to give causal estimates, detect heterogeneity and correct for outliers. RESULTS: We observed consistent positive causal effects of IL-18 on all three major outcomes using three-sample MR, with meta-analyses odds ratios (ORs) equal to 1.240 (IBD), 1.199 (CD) and 1.274 (UC) respectively. The two-sample MR demonstrated similar results. Moreover, genetically predicted IL-1Ra is inversely associated with the risk of IBD/UC/CD with ORs equal to 0.915 (IBD), 0.902 (CD) and 0.899 (UC) respectively in meta-analyses. CONCLUSIONS: This study suggested genetically predicted IL-18 and IL-1Ra level are causally associated with an increased and decreased risk of IBD and subtypes.
Assuntos
Doenças Inflamatórias Intestinais , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-18/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Doenças Inflamatórias Intestinais/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-18/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-1/genéticaRESUMO
Although pressure therapy (PT) represents the standard care for prevention and treatment of hypertrophic scar (HS) from burns, its practice is largely based on empirical evidence and its effectiveness remains controversial. To clarify the effect of PT (15-25 mmHg) for HS, we performed the systematic review and meta-analysis. Several electronic databases were screened to identify related randomized controlled trials (RCTs). 12 RCTs involving 710 patients with 761 HS resulting from burn injuries were included. Compared with non/low-PT, cases treated with PT (15-25 mmHg) showed significant differences in Vancouver Scar Scale score (MD = -0.58, 95% CI = -0.78--0.37), thickness (SMD = -0.25, 95% CI = -0.40--0.11), brightness (MD = 2.00, 95% CI = 0.59-3.42), redness (MD = -0.79, 95% CI = -1.52--0.07), pigmentation (MD = -0.16, 95% CI = -0.32--0.00) and hardness (SMD = -0.65, 95% CI = -1.07--0.23). However, there was no difference in vascularity (MD = 0.03, 95% CI = -0.43-0.48). Our analysis indicated that patients with HS who were managed with PT (15-25 mmHg) showed significant improvements. Due to limitations, more large and well-designed studies are needed to confirm our findings and the side-effects of the PT may also need to be evaluated.