Interleukin-37 is down-regulated in serum of patients with severe coronavirus disease 2019 (COVID-19)

Abstract

Pro-inflammatory and anti-inflammatory cytokines are indicated to play a prominent role in mediating the immunopathogenesis of coronavirus disease 19 (COVID-19). Interleukin (IL-37) is one of the anti-inflammatory cytokines that has been proposed to be involved in disease progression but the data are not overwhelming. Therefore, a case-control study was performed to analyze IL-37 levels in serum of 100 patients with severe COVID-19 and 100 blood donors (control group). Median age was significantly higher in COVID-19 cases than in controls. Stratification by gender, body mass index and ABO and Rh blood group systems showed no significant differences between patients and controls. Chronic diseases (cardiovascular and diabetes) were observed in 57.0% of patients. Serum levels of IL-37 and vitamin D were significantly decreased in patients compared to controls. The low level of IL-37 was more pronounced in males, overweight/obese cases, blood group B or AB cases, Rh-positive cases, and cases with no chronic disease. Low producers of IL-37 were more likely to develop COVID-19 (odds ratio = 2.66; 95% confidence interval = 1.51–4.70; corrected probability = 0.015). Receiver operating characteristic curve analysis demonstrated that a low serum level of IL-37 was a good predictor of COVID-19. Spearman's rank correlation analysis showed that IL-37 and vitamin D were significantly correlated. In conclusion, IL-37 was down-regulated in serum of patients with severe COVID-19 compared to controls. This down-regulation may be associated with an increased risk of disease. Gender, body mass index, blood groups and chronic disease status may also affect IL-37 levels.

Interleukin-37: A Link Between COVID-19, Diabetes, and the Black Fungus

“…The data revealed that SNP rs3811046 detection was significantly higher in patients (61%) when compared to controls (38.0%), which was also the case with SNP rs3811047 (patients 39% vs. controls 24%). In contrast to the previous findings, a more recent study showed that IL-37 expression was suppressed in COVID-19 patients but was prominent in obese patients ( Ahmed and Ad’hiah, 2021b ). Therefore, it is evident that low IL-37 plasma levels could be used as COVID-19 severity marker.…”

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19

“…However, in another study, Ahmed AA and Ad'hiah AH demonstrated lower serum levels of IL-37 and its possible association with a higher risk of disease in COVID-19 patients. Additionally, IL-37 was significantly correlated with vitamin D levels [ 231 ]. Second, they discovered that mutations of the IL37 genes are also associated with the susceptibility to the COVID-19 [ 232 ].…”

Evaluation of interleukin‐38 levels in serum of patients with coronavirus disease 2019

“… 22 Recently, IL‐37, an anti‐inflammatory cytokine functionally related to IL‐38, showed low levels in serum of severely ill COVID‐19 patients, and accordingly it has been suggested that low levels of IL‐37 are associated with disease risk. 10 Moreover, lower levels of IL‐38 were found in severely ill patients compared to patients with nonsevere disease. 11 In the current study, increased levels of IL‐38 were found in severe/critical patients over 50 years of age.…”

“…Accordingly, it has been proposed that IL‐38 can ameliorate inflammation by inhibiting the production of certain proinflammatory cytokines such as IL‐17 and IL‐22 22 . Recently, IL‐37, an anti‐inflammatory cytokine functionally related to IL‐38, showed low levels in serum of severely ill COVID‐19 patients, and accordingly it has been suggested that low levels of IL‐37 are associated with disease risk 10 . Moreover, lower levels of IL‐38 were found in severely ill patients compared to patients with nonsevere disease 11 .…”

“… 9 Further, the anti‐inflammatory cytokine IL‐37 showed reduced levels in serum of severely ill COVID‐19 patients. 10 A recent study also demonstrated for the first time that IL‐38 is an additional cytokine of this family that showed significantly elevated circulating levels in COVID‐19 patients. The study concluded that IL‐38 may exert a protective role against immune system hyperactivity, and may alleviate induced lung inflammation.…”