Evaluation of interleukins (IL-1α, IL-1Ra, IL-12, IL-17A, IL-31, and IL-33) and chemokines (CXCL10 and CXCL16) in the serum of male patients with ankylosing spondylitis.

BACKGROUND: A case-control study was performed to explore eight pro-inflammatory and anti-inflammatory cytokines, namely interleukin (IL)-1α, IL-1Ra (IL-1 receptor antagonist), IL-12, IL-17A, IL-31, IL-33, CXCL10 (C-X-C motif chemokine ligand 10), and CXCL16, with the aim to understand their role in ankylosing spondylitis (AS) pathogenesis and evaluate their utility as markers to differentiate between diseased and healthy individuals. Among these cytokines, IL-31 and CXCL16 have not been well studied in AS. PATIENTS AND METHODS: The study included 94 male patients with AS and 91 age-matched control males. Interleukin and chemokine levels were measured using ELISA kits. RESULTS: Serum levels of IL-17A, CXCL10, and CXCL16 were significantly elevated in patients compared to controls, while IL-31 levels were significantly decreased in patients. IL-17A, CXCL10, and CXCL16 were associated with an increased risk of AS, while IL-31 was associated with a decreased risk of disease (odds ratio = 1.22, 1.78, 1.14, and 0.89, respectively). As indicated by the area under the curve (AUC), IL-17A, IL-31, CXCL10, and CXCL16 were potential markers to differentiate between AS patients and controls (AUC = 0.877, 0.735, 0.8, and 0.7, respectively). IL-1α, IL-1Ra, IL-12, and IL-33 levels showed no significant variations between patients and controls. CONCLUSIONS: Among the eight cytokines examined, IL-17A, CXCL10, and CXCL16 were up-regulated in the serum of AS patients, while IL-31 was down-regulated. The levels of IL-1α, IL-1Ra, IL-12, and IL-33 showed no significant differences between patients and controls. Serum levels of all cytokines were not affected by disease duration, HLA-B27 positivity, or disease activity.

Interleukin-38 promoter variants and risk of COVID-19 among Iraqis.

Coronavirus disease-19 (COVID-19) has recently emerged as a respiratory infection with a significant impact on health and society. The pathogenesis is primarily attributed to a dysregulation of cytokines, especially those with pro-inflammatory and anti-inflammatory effects. Interleukin-38 (IL-38) is a recently identified anti-inflammatory cytokine with a proposed involvement in mediating COVID-19 pathogenesis, while the association between IL38 gene variants and disease susceptibility has not been explored. Therefore, a pilot study was designed to evaluate the association of three gene variants in the promoter region of IL38 gene (rs7599662 T/A/C/G, rs28992497 T/C and rs28992498 C/A/T) with COVID-19 risk. DNA sequencing was performed to identify these variants. The study included 148 Iraqi patients with COVID-19 and 113 healthy controls (HC). Only rs7599662 showed a significant negative association with susceptibility to COVID-19. The mutant T allele was presented at a significantly lower frequency in patients compared to HC. Analysis of recessive, dominant and codominant models demonstrated that rs7599662 TT genotype frequency was significantly lower in patients than in HC. In terms of haplotypes (in order: rs7599662, rs28992497 and rs28992498), frequency of CTC haplotype was significantly increased in patients compared to HC, while TTC haplotype showed significantly lower frequency in patients. The three SNPs influenced serum IL-38 levels and homozygous genotypes of mutant alleles were associated with elevated levels. In conclusion, this study indicated that IL38 gene in terms of promoter variants and haplotypes may have important implications for COVID-19 risk.