Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

Ozer, Erdem Kamil; Göktaş, Mustafa Tuğrul; Kılınç, İbrahim; Toker, Aysun; Barışkaner, Hülagü; Uğurluoğlu, Ceyhan; İskit, Alper B.

doi:10.1139/cjpp-2016-0628

Cited by 9 publications

(5 citation statements)

References 31 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protective effects of rPPE18 were, therefore, demonstrated in two models of sepsis. Ability to reduce TNF-a and attenuate organ damage in CLP-induced sepsis correlates with increased survival as has been demonstrated previously (13,14,(70)(71)(72). rPPE18 was able to consistently reduce elevated levels of TNF-a in E. coli BL21induced and CLP-induced sepsis when administered therapeutically.…”

Section: Discussionsupporting

confidence: 75%

Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis

Ahmed

Dolasia

Mukhopadhyay

2018

The Journal of Immunology

View full text Add to dashboard Cite

PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis.

show abstract

Section: Discussionsupporting

confidence: 75%

Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis

Ahmed

Dolasia

Mukhopadhyay

2018

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In the study performed by Ozer et al [ 12 ], the administration of IFX (7 mg/kg, i.p.) 24 h prior to CLP surgery increased the survival rate to 57% in comparison to our results, which showed that the administration of IFX (5 mg/kg, s.c.) 2 h following the induction of sepsis improved survival to 37.5%.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies have investigated the effect of blockading inflammatory cytokines such as TNF-α, and others have looked at the effect of inhibiting COX-2 activity against sepsis. For example, Ozer, et al [ 12 ] found that the survival of septic animals given infliximab (IFX), an antibody against TNF-α, as a prophylactic treatment prior to cecal ligation and puncture (CLP) surgery increased. Another study [ 13 ] showed that the administration of celecoxib (CLX), a selective COX -2 inhibitor, after CLP also resulted in a reduced mortality rate.…”

Section: Introductionmentioning

confidence: 99%

Effect of Celecoxib and Infliximab against Multiple Organ Damage Induced by Sepsis in Rats: A Comparative Study

et al. 2022

View full text Add to dashboard Cite

In cases of sepsis, the immune system responds with an uncontrolled release of proinflammatory cytokines and reactive oxygen species. The lungs, kidneys, and liver are among the early impacted organs during sepsis and are a direct cause of mortality. The aim of this study was to compare the effects of infliximab (IFX) and celecoxib (CLX) on septic rats that went through a cecal ligation and puncture (CLP) surgery to induce sepsis. This study included four groups: sham, CLP (untreated), and CLP-treated with CLX or IFX. The administration of “low dose” CLX or IFX was performed after 2 h following the induction of sepsis. Twenty-four hours following the induction of sepsis, the rats were sacrificed and blood samples were collected to evaluate kidney, liver, and lung injuries. MDA and NOx content, in addition to SOD activity and GSH levels, were evaluated in the tissue homogenates of each group. Tissue samples were also investigated histopathologically. In a separate experiment, the same groups were employed to evaluate the survival of septic rats in a 7-day observation period. The results of this study showed that treatment with either CLX or IFX ameliorated the three organs’ damage compared to septic-untreated rats, decreased oxidative stress, enhanced the antioxidant defense, and reduced serum cytokines. As a result, a higher survival rate resulted: 62.5% and 37.5% after the administration of CLX and IFX, respectively, compared to 0% in the CLP group after 7 days. No significant differences were observed between the two agents in all measured parameters. Histopathological examination confirmed the observed results. In conclusion, CLX and IFX ameliorated lung, kidney, and liver injuries associated with sepsis through anti-inflammatory and antioxidant actions, which correlated to the increase in survival observed with both of them.

show abstract

“…In addition, overwhelmed cytokine production during sepsis is also considered detrimental. In fact, lower mortality was observed in rats exposed to LPS and treated with a monoclonal antibody against TNF-α [20], and beneficiary effects were also observed for anti-IL-1β as well as anti-IL-6 antibody treatment in other experimental models of sepsis [21,22].…”

Section: Discussionmentioning

confidence: 99%

Hyperbilirubinemia in Gunn Rats Is Associated with Decreased Inflammatory Response in LPS-Mediated Systemic Inflammation

Valášková

Dvořák

Leníček

et al. 2019

IJMS

View full text Add to dashboard Cite

Decreased inflammatory status has been reported in subjects with mild unconjugated hyperbilirubinemia. However, mechanisms of the anti-inflammatory actions of bilirubin (BR) are not fully understood. The aim of this study is to assess the role of BR in systemic inflammation using hyperbilirubinemic Gunn rats as well as their normobilirubinemic littermates and further in primary hepatocytes. The rats were treated with lipopolysaccharide (LPS, 6 mg/kg intraperitoneally) for 12 h, their blood and liver were collected for analyses of inflammatory and hepatic injury markers. Primary hepatocytes were treated with BR and TNF-α. LPS-treated Gunn rats had a significantly decreased inflammatory response, as evidenced by the anti-inflammatory profile of white blood cell subsets, and lower hepatic and systemic expressions of IL-6, TNF-α, IL-1β, and IL-10. Hepatic mRNA expression of LPS-binding protein was upregulated in Gunn rats before and after LPS treatment. In addition, liver injury markers were lower in Gunn rats as compared to in LPS-treated controls. The exposure of primary hepatocytes to TNF-α with BR led to a milder decrease in phosphorylation of the NF-κB p65 subunit compared to in cells without BR. In conclusion, hyperbilirubinemia in Gunn rats is associated with an attenuated systemic inflammatory response and decreased liver damage upon exposure to LPS.

show abstract

Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

Cited by 9 publications

References 31 publications

Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis

Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis

Effect of Celecoxib and Infliximab against Multiple Organ Damage Induced by Sepsis in Rats: A Comparative Study

Hyperbilirubinemia in Gunn Rats Is Associated with Decreased Inflammatory Response in LPS-Mediated Systemic Inflammation

Contact Info

Product

Resources

About