The Role of IL-6, TNF-α, and VDR in Inhibiting the Growth of Salmonella Typhi: in vivo Study

Abstract

Background and aim: The prevalence of typhoid fever is reportedly high, especially in Asia. When a pathogen enters the human body, there are markers in the form of molecules that will be known by the innate immune system. Specific molecular markers of gram negative bacteria, which are Lipopolysaccharides (LPS) and Toll-Like receptors-4 will interact with LPS. The binding between LPS and TLR-4 will give rise to activation signals that will activate innate immune cells. Immune cells will release a number of proinflammatory cytokines, such as TNF-α, IL-1, and IL-6. While Vitamin D Receptors (VDR) are expressed in large amounts in tumor tissue and infected cells. This study aimed to prove the role of IL-6, TNF-α, and VDR in inhibiting bacterial growth in mice that have been induced by S.Typhi. Methods: This research was a real experimental pre-post test design to investigate the level of IL-6, TNF-α and VDR in suppressing the growth of bacteria in the peritoneal fluid of S. Typhi, male, mice BALB/c. Mice were divided into three groups comprised of 10 mice each. All mice in groups A and B were intraperitoneally inoculated with S. Typhi strain Thy1 in study day 0. Group A was treated with antibiotic Levofloxacine, on study day 4th. Another study group, group B, was used as a placebo and received aquades on study day 4th. While group C as a control was not inoculated with S. Typhi. Blood samples from three groups for the calculation of serum Il-6, TNF-α, and VDR were collected. This examination was taken four times; at baseline, 4th day, 10th day, and 30th day. For the calculation of bacterial colony, peritoneal fluid retrieval was collected three times, which is on 4th day, 10th day, and 30th day. Results: A repeated measure ANOVA in group A (antibiotic) and group B (placebo) group showed that mean IL-6, TNF-α, and VDR level differed statistically significant between times (p-value 0.000). There was a strong negative correlation between bacterial colony count and VDR level, which was statistically significant in both groups (group A; r = -0.875, p-value = 0.000 vs group B; r = -0.470, p-value = 0.002). IL-6 and TNF-α didn't give significant statistical correlation with bacterial colony count. Conclusion: VDR, IL-6, and TNF-α play an important role in killing bacteria. From the results of this study, IL-6 level is related to the number of bacterial colonies, the lower the IL-6 level, the less the number of bacterial colonies. Similarly, TNF-α levels have a positive correlation with the number of bacterial colonies. While VDR levels are also related to the number of bacterial colonies, the higher the VDR level, the lower the number of bacterial colonies.

Natural Resistance Associated Macrophage Protein-1 Expression in Salmonella typhi Infection with Acute Recurrence State of Typhoid Fever in Endemic Areas, Indonesia

“…Previous study revealed that other host susceptibility gene such as Vitamin D Receptor (VDR) could inhibit the growth of Salmonella typhi in vivo. [37].…”

“…Several study related with immune response in typhoid fever like the role of IL6, TNF alpha in inhibit of S. typhi in vitro dan In some cases salmonella typhi infection may affect TLR4 expression in vivo [12,13,14].…”

Evaluation of the efficiency of ciprofloxacin against S. Typhi by altering the production of cytokines in acute typhoid fever in patients at Al-Diwaniyah Hospitals, Iraq

“…Following S. Typhi infection, signalling pathways within cells trigger the release of cytokines (Keuter et al, 1994). Importantly, IL-6 is an essential multifunctional cytokine that exerts its proinflammatory and anti-inflammatory properties (Febriza et al, 2020). This cytokine derives from different cells of the human body, such as endothelial cells, lymphocytes, macrophages, astrocytes and ischemic myocytes; thus, it can regulate many pathological and physiological activities (Niculet et al, 2021).…”

“…The host immune system recognises the causative agent Salmonella via recognition receptors, importantly Toll-like receptors (TLR) (Kurtz et al, 2017). This could promote downstream signalling pathways and activate an inflammatory response by releasing cytokines such as TNF-a, IL-1, IL-6 and IL-8 (Andrade and Andrade Júnior, 2003;Febriza et al, 2020). These crucial mediators including cytokines play a key role in attracting phagocytosis cells like macrophages, polymorphonuclear neutrophils (PMNs) and monocytes, which are involved in bacterial inhibition (Febriza et al, 2020).…”

In vivo and in vitro inhibition effect of propolis on Klebsiella pneumoniae : A review

“…Numerous studies have examined the use and effects of traditional medicines for various diseases [ [1] , [2] , [3] , [4] , [5] ], including the effects of herbal medicines on infectious diseases, such as candidiasis [ [6] , [7] , [8] ], typhoid fever [ [9] , [10] , [11] , [12] , [13] , [14] ], toxoplasmosis [ [15] , [16] , [17] ], gingivitis [ 18 , 19 ], vaginitis [ 20 ], and the human immunodeficiency virus (HIV) [ 21 , 22 ], and noninfectious diseases such as diabetes [ 23 ].…”