Serum Inflammatory Factors TNF-α Research Articles

Efficacy of Daiwenjiu ointment on the treatment of cervical spondylosis with nerve root type caused by cold dampness obstruction

Objective This study aimed to assess the clinical efficacy of Daiwenjiu ointment in the treatment of cervical spondylosis with cold dampness obstruction nerve root type. Methods A retrospective analysis was conducted on a cohort of 110 patients diagnosed with cervical spondylotic radiculopathy. Based on the treatment method, the patients were divided into two groups. The control group received electroacupuncture treatment, while the observation group received a combination of Daiwenjiu ointment and electroacupuncture treatment. The outcome measures included Japanese Orthopedic Association (JOA) scores for cervical spine function, Simplified McGill Pain Questionnaire (SF-MPQ) scores, and changes in serum inflammatory factors TNF-α and IL-1β. Results Following treatment, the JOA score in the observation group increased from 9.45 ± 1.35 to 14.82 ± 1.29 after treatment, indicating better recovery of cervical spine function compared to the control group (p < 0.001). The SF-MPQ score in the observation group decreased to 18.25 ± 3.80 after treatment, while it remained at 30.20 ± 4.30 in the control group. This difference between the groups was statistically significant (p < 0.001). Furthermore, the observation group demonstrated a significant decrease in serum levels of TNF-α and IL-1β after treatment compared to the control group (p < 0.001). Conclusion Daiwenjiu ointment exhibits significant therapeutic effects in patients with cold dampness obstruction nerve root type cervical spondylosis. It effectively improves cervical function, reduces pain, and downregulates inflammatory cytokine levels.

Network Meta-analysis of efficacy of seven Chinese patent medicines in treatment of inflammatory response in chronic glomerulonephritis

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in chronic glomerulonephritis(CGN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with CGN was retrieved from databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to March 2023. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 and RevMan 5.4.1 software were used to analyze the data of the literature that met the quality standards. Finally, 71 RCTs were included, involving 7 Chinese patent medicines. The total sample size was 6 880 cases, including 3 441 cases in the test group and 3 439 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenyanshu Capsules/Granules/Tablets+conventional western medicine, Huangkui Capsules+conventional western medicine, and Bailing Capsules+conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Huangkui Capsules+conventional wes-tern medicine, and Bailing Capsules+conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Bailing Capsules+conventional western medicine, and Shenyan Kangfu Tablets+conventional western medicine.(4) In terms of reducing 24hUTP, the top 3 optimal interventions according to SUCRA were Shenyan Kangfu Tablets+conventional western medicine, Bailing Capsules+conventional western medicine, and Huangkui Capsules+conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Bailing Capsules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Yishen Huashi Granules+conventional western medicine.(6) In terms of reducing BUN, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Bailing Capsules+conventional western medicine.(7) In terms of improving the clinical total effective rate, the top 3 optimal interventions according to SUCRA were Huangkui Capsules+conventional western medicine, Kunxian Capsules+conventional western medicine, and Yishen Huashi Granules+conventional western medicine. The results showed that the combination of conventional western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of conventional western medicine and Chinese patent medicine was superior to conventional western medicine alone in reducing Scr, BUN, and 24hUTP, and improving the clinical total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

Palmatine attenuates LPS-induced neuroinflammation through the PI3K/Akt/NF-κB pathway.

To investigate the key molecular mechanisms of palmatine for the treatment of neuroinflammation through modulation of a pathway using molecular docking, molecular dynamics (MD) simulation combined with network pharmacology, and animal experiments. Five alkaloid components were obtained from the traditional Chinese medicine Huangteng through literature mining. Molecular docking and MD simulation with acetylcholinesterase were used to screen palmatine. At the animal level, mice were injected with LPS intracerebrally to cause a neuroinflammatory model, and the Morris water maze experiment was performed to examine the learning memory of mice. Anxiety levels were tested using the autonomous activity behavior experiment with the open field and elevated behavior experiments. HE staining and Niss staining were performed on brain tissue sections to observe morphological lesions and apoptosis; serum was examined for inflammatory factors TNF-α, IL-6, and IL-1β; Western blot was performed to detect the protein expression. The expression of PI3K/AKT/NFkB signaling pathway-related proteins was examined by Western blot. The results of network pharmacology showed that the screening of palmatine activation containing the PI3K/Akt/NFkB signaling pathway exerts antineuroinflammatory effects. Results from behavioral experiments showed that Pal enhanced learning memory in model mice, improved anxiety behavior, and significantly improved brain damage caused by neuroinflammation. The results of HE staining and Niss staining of brain tissue sections showed that palmatine could alleviate morphological lesions and nucleus damage in brain tissue. Palmatine improved the levels of serum inflammatory factors TNF-α, IL-6, and IL-1β. SOD, MDA, CAT, ACH, and ACHE in the hippocampus were improved. Western blot results showed that palmatine administration ameliorated LPS-induced neuroinflammation through the PI3K/Akt/NFkB pathway.

Network Meta-analysis of efficacy of Chinese patent medicine in treatment of inflammatory response in diabetic nephropathy

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in diabetic nephropathy(DN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with DN was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from database inception to October 2022. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 software and RevMan 5.4.1 were used to analyze the data of the literature that met the quality standards. Finally, 53 RCTs were included, involving 6 Chinese patent medicines. The total sample size was 4 891 cases, including 2 449 cases in the test group and 2 442 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Jinshuibao Capsules + conventional western medicine, and Niaoduqing Granules + conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Shenshuaining Capsules/Granules/Tablets + conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(4) In terms of reducing UAER, the top 3 optimal interventions according to SUCRA were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Huangkui Capsules + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granules + conventional wes-tern medicine, and Tripterygium Glycosides Tablets + conventional western medicine.(6) In terms of reducing BUN, the first 3 optimal interventions according to SUCRA were Niaoduqing Granules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Huangkui Capsules + conventional western medicine.(7) In terms of improving the clinical total effective rate, the first 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granu-les + conventional western medicine, and Huangkui Capsules + conventional western medicine. The results showed that the combination of western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of western medicine and Chinese patent medicine was superior to western medicine alone in reducing Scr, BUN, and UAER, and improving the total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice

Ethnopharmacological relevanceThe dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. Aim of the studyThis study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). Materials and methodsModel mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. ResultsIn vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1β, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. ConclusionsThese data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent.

PI3K-Akt signaling pathway based on network pharmacology for the anti-Alzheimer's disease effect of licorice stem flavonoids.

Active ingredients were screened by TCMSP and swissADME, meanwhile, PharmMapper combined with UniProt database was used to predict the active ingredient target information, GeneCard database was employed to obtain Alzheimer's disease (AD)-related genes, Cytoscapes 3.7.2 software was utilized to map the active ingredient-target effect. Besides, Cytoscapes 3.7.2 software Bisogenet and Cyto NCA plug-in combined with STRING platform were utilized to map the protein-protein interaction (PPI) network, DAVID was employed for GO annotation, while KEGG plug-in was used for KEGG pathway enrichment. Mice were tested for inflammatory damage induced by intracerebral injection of lipopolysaccharide (LPS), as well as learning memory and anxiety by water maze and open field tests. In addition, the expression of Caspase-3 and Caspase-9, together with inflammatory factors TNF-α, IL-6, and IL-1β was analyzed in serum. The expression levels of proteins related to PI3K-Akt signaling pathway in the brain were detected by Western blot (WB) assay. According to the results of network pharmacology, there were 35 active ingredients of licorice stem and leaf flavonoids screened, which exerted the anti-Alzheimer's disease (AD) effects via 67 targets and activated 41 signaling pathways including the PI3K-Akt pathway. Furthermore, Behavioural results revealed that Licorice stem and leaf flavonoids improved the learning and memory abilities of model mice and significantly improved the anxiety caused by inflammatory brain damage. Moreover, as suggested by HE staining and TUNEL staining of brain sections, Glycyrrhiza glabra stem and leaf flavonoids alleviated morphological lesions and cell nuclear damage in brain tissue. Results: of brain homogenate supernatant assay demonstrated that Glycyrrhiza glabra stem and leaf flavonoids had a significant effect on the levels of oxidative indicators superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), acetylcholine (Ach), acetylcholinesterase (AchE), Caspase-3, Caspase-9 and serum inflammatory factors TNF-α, IL-6 and IL-1β. Additionally, WB assay results indicated that the PI3K-Akt signaling pathway was activated.

Novel quinoline-based derivatives: A new class of PDE4B inhibitors for adjuvant-induced arthritis

A total of 31 quinoline-based derivatives were designed and synthesized to develop novel anti-inflammatory drugs. After the toxicity of synthetic compounds to RAW264.7 cells were evaluated in vitro, their anti-inflammatory activity was assessed by inhibiting lipopolysaccharide (LPS)-induced NO production levels in the RAW264.7 cells. Among the derivatives, compound f4 had the best anti-inflammatory activity, which could reduce the production of pro-inflammatory cytokines NO, IL-1β, and TNF-α with corresponding IC50 values of 20.40 ± 0.94, 18.98 ± 0.21 and 23.48 ± 0.46 μM. Western blot showed that f4 could inhibit the expression of LPS-induced inflammatory mediators iNOS and COX-2. Molecular docking showed that f4 could also enter the PDE4B receptor binding pocket, and the cellular thermal shift assay method indicated that the PDE4B protein bound to f4 had increased stability. Meanwhile, the inhibitory effect of this compound on the PDE4B enzyme (IC50 = 0.94 ± 0.36 μM) was comparable to that of the positive drug rolipram (IC50 = 1.04 ± 0.28 μM). Finally, in vivo studies showed that f4 could improve the degree of foot swelling and knee joint pathology in adjuvant-induced arthritic rats and decrease the levels of serum inflammatory factors TNF-α and IL-1β in a dose-dependent manner. Therefore, the development and design of quinoline-based derivatives for anti-inflammatory applications could be considered opportunities and challenges.

Changes in intestinal florae and serum inflammation in rheumatoid arthritis rats and the effects of probiotics.

The aim of this study was to explore the changes in intestinal florae and serum inflammation in rats with rheumatoid arthritis (RA), and to investigate the effects of probiotics. A total of 30 Sprague Dawley (SD) rats were randomly divided into three groups, namely, control group, model group, and probiotic group. The rats in the model group were prepared into models of collagen II-induced arthritis. Meanwhile, the rats in probiotic group were treated with probiotics for 6 weeks via intragastric administration in addition to the treatment in the model group. Next, the feces of rats in the control group, model group, and probiotic group were sampled to detect the composition of intestinal florae. In addition, peripheral blood was collected from rats to determine the changes in the content of inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β through enzyme-linked immunosorbent assay (ELISA). Compared with the control group, the levels of serum inflammatory factors TNF-α, IL-6 and IL-1β were significantly upregulated in the model group (p<0.05). This suggested successful modeling. However, they decreased notably in probiotic group when compared with the model group (p<0.05), indicating that probiotics could inhibit inflammatory response in rats. The levels of microbes Bacteroidetes, Streptococcus and Clostridiales were significantly higher in the control group (p<0.05). The levels of Ruminococcaceae, Asoccbarobacler, Coriobacteriaceae, and fecal anaerobic coryneform bacteria were remarkably higher in the model group (p<0.05). Meanwhile, the levels of Porphyromonadaceae, Barnsiella, Actinobacteria, Alloscardovia, Bifidobacteria and Parabacteroides were remarkably higher in probiotic group (p<0.05). The intestinal level of Bacteroides was the highest in rats of control group, which decreased significantly in the model group (p=0.000). However, the intestinal level of Bacteroides in probiotic group was overtly higher than that in the model group (p=0.000), whereas was lower than the control group. The intestinal level of Bifidobacteria in the model group was significantly lower than that in the control group (p=0.024). However, it was evidently higher in the probiotic group than that in both model group and control group (p=0.000). The intestinal level of Asoccbarobacler was remarkably higher in the model group than that in control group (p=0.005). However, it was lower in probiotic group than that in model group (p=0.003), showing the highest in model group. There was an evidently negative correlation between Firmicuteria and Clostridium (r=-0.82, p=0.000), and a positive association between Firmicuteria and Bacteroides (r=0.77, p=0.000). Bacteroides was negatively correlated with Clostridium (r=-0.89, p=0.002) and Enterococcus (r=-0.63, p=0.021). In addition, Enterococcus had a highly positive correlation with Clostridium (r=0.6, p=0.001). Evident changes in intestinal florae and serum inflammation are detected in rats with RA, and such changes can be partially reversed by probiotics.

Protective effect of electro-acupuncture on liver ischemia-reperfusion injury in rats.

Liver ischemia-reperfusion injury is an important clinical complication in which excessive inflammation is a key factor; however, few studies have provided effective means of its regulation. As previous studies suggested that electro-acupuncture (EA) is able control excessive inflammation, the present study aimed to explore its effects on liver ischemia-reperfusion injury in experimental rats. The animals were randomly divided into surgery and sham groups, which were further divided into four sub-groups, including a non-treatment (NT), a non-point acupuncture (NPA), the non-selective nicotinic acetylcholine receptor (AChR) agonist 1,1-dimethyl-4-phenyl L-pioperazinium iodide (DMPPI) and an EA group. The alanine aminotransferase (ALT), serum cytokine and myeloperoxidase (MP) levels and the tissue pathology were evaluated after 90 min of ischemia followed by a 4, 8 or 24 h reperfusion. The results demonstrated that EA and DMPPI suppressed serum ALT elevation at 4 and 8 h reperfusion, whereas NPA did not. I/R induced hepatocellular necrosis, and cytoplasmic vacuolization and sinusoidal congestion was ameliorated by EA treatment after an 8 and 24 h reperfusion. In addition, EA also inhibited liver neutrophil accumulation, evidenced by a decreased MPO level at 8 h reperfusion. EA also suppressed the release of serum inflammatory factors TNF-α and IL-6 for the duration of reperfusion. However, little influence on IL-10 was observed. Mechanistically, vagus block by subphrenic vagotomy or mecamylamine hydrochloride abolished EA effect on liver damage, neutrophil accumulation and inflammatory factor release. In conclusion, it was demonstrated that EA protects the liver against I/R induced injury by inhibiting the inflammatory response, which is associated with the vagus.

Correlation between serum inflammatory factors TNF-α, IL-8, IL-10 and Henoch-Schonlein purpura with renal function impairment.

The changes of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10) in the serum of Henoch-Schonlein purpura nephritis (HSPN) patients were analyzed to explore the correlation between the above inflammatory factors and progression of the disease. The present study used the double antibody sandwich enzyme-linked immunosorbent assay (ELISA) method to detect the serum levels of TNF-α, IL-8, IL-10 and urine protein in 112 cases of patients with Henoch-Schonlein purpura (HSP), including 54 cases of HSP combined with renal function impairment (group HSPN), and 58 cases not combined with renal function impairment (NHSPN), as well as 50 healthy patients who were selected as the control group. The concentration of TNF-α, IL-8, and IL-10 in the serum of HSP patients were higher than that of the control group, and the difference was statistically significant (P<0.05). There was no significant difference in the levels of IL-10, and IL-8 between the HSPN group and the NHSPN group (P>0.05), but the level of TNF-α in the serum of HSPN group was significantly higher than that of NHSPN group (P<0.05). TNF-α, IL-8 and IL-10 levels of the acute nephritis, chronic nephritis and nephrotic syndrome groups were all higher than the simple proteinuria group. In addition, the levels of the three factors of the acute nephritis group were all higher than those of the chronic nephritis and nephrotic syndrome groups (P<0.05). IL-8, IL-10, and TNF-α were positively correlated with the urinary protein levels. The results indicated that the levels of serum TNF-α, IL-8 and IL-10 are correlated with HSPN, and serum TNF-α concentration can be used as an indicator of the severity of HSPN.

Therapeutic effect of percutaneous endoscopic lumbar discectomy on lumbar disc herniation and its effect on oxidative stress in patients with lumbar disc herniation.

This study investigated the therapeutic effect of percutaneous endoscopic lumbar discectomy on lumbar disc herniation, and explored its effect on oxidative stress in patients with lumbar disc herniation. One hundred and ten patients with lumbar disc herniation were selected in The Affiliated People's Hospital of Shanxi Medical University from May 2015 to May 2016. Patients were divided into control group (n=50) and observation group (n=60) according to different surgical methods. Patients in control group were subjected to traditional open discectomy, while patients in observation group were treated with percutaneous endoscopic lumbar discectomy. Surgical-related indicators, ODI and VAS scores before and 3 months after surgery, serum inflammatory factors and oxidative stress indicators were compared between 2 groups. There was no significant difference in operation time between the groups. Blood loss, incision size and time of bed rest in observation group were better than those in control group (P<0.05). Compared with preoperative levels, ODI and VAS scores of the two groups were significantly reduced at 3 months after surgery, but the scores of observation group were significantly higher than those of control group (P<0.05). There were no significant differences in the levels of serum inflammatory factors TNF-α and CRP and oxidative stress indicators MDA, MPO, SOD and TAC between the two groups before surgery (P>0.05). Levels of serum inflammatory factors TNF-α and CRP and oxidative stress indicators MDA and MPO were significantly lower and levels of oxidative stress indicators SOD and TAC were significantly higher in observation group than in control group (P<0.05). Therefore, treatment of lumbar disc herniation with percutaneous endoscopic lumbar discectomy has the advantages of small trauma, less blood loss and fast recovery, and can effectively improve the dysfunction, reduce pain and serum levels of inflammatory factors, and improve the levels of oxidative stress indicators, thereby improving the surgical results. Thus, this method should be considered for wide-use.

Chronic inflammation and pain in a tumor necrosis factor receptor (TNFR) (p55/p75-/-) dual deficient murine model

Many aspects of tissue damage after acute or chronic inflammatory reactions can be attributed directly to the concomitant biosynthesis and release of inducible early proinflammatory cytokine tumor necrosis factor alpha (TNFα). Conversely, systemic inflammation is impacted by the consequences of tissue damage. Dysregulated TNFα contributes to numerous pathophysiologic conditions including inflammatory bowel disease (IBD) and arthritis. Inflammatory stimuli trigger proteolytic cleavage and shedding of extracellular domains of TNFα receptors giving rise to 2 soluble fragments (p55 soluble tumor necrosis factor receptor 1 (sTNFR1) and p75 sTNFR2) that block the additional binding, activity, and synthesis of TNFα. We hypothesized that absence of sTNFR inhibitory feedback control would result in accumulated high levels of TNFα and other inflammatory factors promoting the cardinal signs of chronic inflammation and pain. The current study reports a translational murine model of chronic arthritis precipitated by 2 consecutive inflammatory insults. The "double hit" procedures provoke a chronic inflammatory response and pain-related behaviors in mice that are dually deficient in p55 (TNFR1) and p75 (TNFR2). The inflammation- and pain-related behaviors are transient in similarly treated wild-type (WT) mice. The complete Freund's adjuvant (CFA) method was used initially to induce knee joint inflammation, tactile mechanical and heat hypersensitivity, and gait disturbance. After these transient effects of the insult were resolved, a recrudescence persisting at least through 23 weeks was promoted by gastrointestinal (GI) insult with dilute intracolonic mustard oil (MO) only in the mutant mice and was reversed by a P2X7 antagonist. A serum proteome profiling analysis revealed high levels of serum inflammatory factors TNFα, regulated upon activation normally T-cell expressed and secreted (RANTES), chemokine (C-X-C motif) ligand 9 [CXCL9 (MIG)], chemokine (C-X-C motif) ligand 10 [CXCL10 (IP-10)], and chemokine (C-C motif) ligand 2 [CCL2 (MCP-1)]. These data suggest that impaired signaling of TNFα as a result of the deficit of the 2 protective soluble p55 and p75 sTNFR inhibitory factors plays a pivotal role in the reactivation of the immune response to GI insult that can produce recrudescence of inflammatory injury and a chronic pain state through promotion of high levels of serum inflammatory factors.