We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-beta)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1beta and TGF-beta. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.
Animals ; Brain/*immunology/*pathology ; Brain Injuries/immunology/*pathology/*veterinary ; Dogs ; Humans ; Interleukin-10/immunology/metabolism ; Interleukin-1beta/immunology/metabolism ; Interleukin-6/immunology/metabolism ; Transforming Growth Factor beta/immunology/metabolism ; Tumor Necrosis Factor-alpha/immunology/metabolism

OBJECTIVETo investigate the changes in the expression of HLA-DR on CD14+ monocytes of burn patients with delayed resuscitation, and to analyze the relationship between it and sepsis.

METHODSTwenty-five patients with total burn surface area over 30% TBSA and delayed resuscitation were enrolled in the study, among which 7 were complicated by sepsis during hospitalization. Peripheral blood was collected on 1, 3, 7, 14 and 28 post-burn days (PBD), and the blood of the patients with sepsis were also collected on the 1 and 2 days after the occurrence of sepsis. Twenty healthy volunteers were enrolled as controls. Expression rate of HLA-DR on CD14+ monocytes was determined by flow cytometry. The level of TNF-alpha and IL-10 were measured by ELISA.

RESULTSExpression rate of HLA-DR antigen on CD14+ monocytes in burn patients without sepsis on 1, 3, 7, 14, 28 PBD were (15 +/- 6)%, (7 +/- 5)%, (26 +/- 17)%, (28 +/- 16)% and (47 +/- 16)%, respectively, which were obviously lower than that of healthy people [(92 +/- 10)%, P < 0.01], and it was also markedly lower on 1 and 2 days after the occurrence of sepsis than that of controls and those of patients without sepsis on 1, 7, 14, 28 PBD (P < 0.01). The positive rate and concentration of TNF-alpha in patients with sepsis were obviously higher than that of healthy people and patients without sepsis (P < 0.05 or P < 0.01). There was a negative correlation between the expression rate of HLA-DR on CD14+ monocytes and IL-10 levels, and it showed significant difference on 1, 7, and 28 PBD (r = -0.9963, -0.7459, -0.8474, respectively, P < 0.01).

CONCLUSIONImmune function is suppressed and proinflammatory mediators are excessively released in severely burn patients after delayed resuscitation, especially when complicated with sepsis. Expression of HLA-DR on CD14+ monocytes may be an useful parameter for monitoring the immune function of burn patients.

Burns ; immunology ; metabolism ; HLA-DR Antigens ; metabolism ; Humans ; Interleukin-10 ; blood ; Lipopolysaccharide Receptors ; metabolism ; Monocytes ; immunology ; metabolism ; Sepsis ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-kappaB), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunction (EID) during the implantation time (namely on pregnancy day 5, 6, 7 and 8) and explored the local immune regulatory effects of Bangdeyun. The gestational mice were randomly divided into normal group, model group and Bangdeyun-treated group. EID models of mice were established by using indomethacin. The endometrial expression of NF-kappaB was detected by immunohistochemistry and Western blotting. IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in the normal group, NF-kappaB and IFN-gamma were weakly expressed and IL-10 was strongly expressed in the endometrium during the whole implantation period. In the model group, the expressions of NF-kappaB and IFN-gamma were increased on pregnancy day 5, 6 and 7, and IL-10 expression decreased during the whole implantation time when compared with those in the normal group (P<0.01 for all). In the Bangdeyun-treated group, little amount of NF-kappaB and IFN-gamma was expressed and IL-10 expression was strong, much the way they were expressed in the normal group (P>0.05). The expressions of NF-kappaB and IFN-gamma were much lower in the Bangdeyun-treated group than those in the model group on pregnancy day 5, 6 and 7 (P<0.01 for all), while the expression of IL-10 was much higher than in the model group during the whole implantation time (P<0.01). It was suggested Bangderun may favor a shift from Th1- to Th2-type immune response, therefore inhibiting the maternal immune rejection, inducing the immune tolerance and improving the fetal implantation.
Drugs, Chinese Herbal/*pharmacology ; Embryo Implantation, Delayed/*drug effects ; Embryo Implantation, Delayed/immunology ; Endometrium/*immunology ; Endometrium/metabolism ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism

OBJECTIVETo investigate the changes in serum levels of Th1- (IL-2 and TNF-alpha) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 (IL-2/IL-10 and TNF-alpha/IL-10) in preeclampsia and in gestational hypertension.

METHODSLevels of IL-2, IL-10 and TNF-alpha were determined with radioimmunoassay in serum samples from 22 women with preeclampsia, 15 women with gestational hypertension and 32 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly.

RESULTThere were no significant differences in serum levels of IL-2, IL-10 and TNF-alpha (P>0.05 for all) among normal pregnancy, gestational hypertension and preeclampsia. The ratio of serum IL-2/IL-10 was significantly higher in preeclampsia than that in controls (P < 0.05), and the ratio of TNF-alpha/IL-10 significantly higher in patients with preeclampsia than that in either controls or gestational hypertension (P<0.025 for both).

CONCLUSIONAlterations of serum cytokine balance with predominance of Th1 immunity were observed in preeclampsia. These associations may offer insight into the pathogenesis of preeclampsia.

Adult ; Female ; Humans ; Hypertension, Pregnancy-Induced ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Pre-Eclampsia ; blood ; Pregnancy ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

This study was aimed to investigate the effects of xenogeneic antigen neu-Fc in combination with the recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and Bacillus Calmette-Guerin (BCG) on the regulation of Th1 and Th2 immune response in vitro. The rat neu L2-S2 domain was engineered as a chimeric protein with human IgG Fc. The eukaryotic expression vector was constructed. The recombinant protein was stably expressed in CHO cells and purified by rProtein A Sepharose Fast Flow column. The recombinant protein was identified by SDS-PAGE and Western blot. Peripheral blood mononuclear cells (PBMNCs) were obtained by means of standard Ficoll separation from the blood of healthy donors. Neu-Fc-induced PBMNC proliferation was tested by MTT. The production of IL-12 and IL-10 was measured by ELISA. The results showed that the level of IL-12 decreased and IL-10 increased after PBMNCs were incubated with MCF-7 cultural supernatant. 10 nmol/L neu-Fc strongly induced the cell proliferation. Compared with neu-Fc or GM-CSF or BCG treatment alone, neu-Fc in combination with GM-CSF and BCG significantly stimulated IL-12 production and inhibited IL-10 production (p < 0.01). It is concluded that the neu-Fc can stimulate the proliferation activity of PBMNCs. neu-Fc, GM-CSF and BCG costimulation efficiently induces Th1 immune response.
Animals ; BCG Vaccine ; immunology ; CHO Cells ; Cricetinae ; Cricetulus ; Granulocyte-Macrophage Colony-Stimulating Factor ; immunology ; Humans ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Rats ; Recombinant Proteins ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo observe the relationship between the contents of interleukin-1beta (IL-1beta), interleukin-4 (IL-4) and interleukin-10 (IL-10) in the seminal plasma of infertile males and sperm function indexes.

METHODSBy radioimmunoassay (RIA), we determined the contents of IL-1beta, IL-4 and IL-10 in the seminal plasma of 126 infertile and 20 normal males. According to the sperm count, the infertile were divided into three groups: Groups A (sperm count > or = 20 x 10(6)/ml), B (sperm count < 20 x 10(6)/ml) and C (azoospermia). Based on sperm vitality and motility, Group A was subdivided into a normal and abnormal vitality group and a normal and decreased motility group. In line with the serum results of antisperm antibody (AsAb) and semen WBC, the infertile males were divided into AsAb positive and negative, and WBC semen and non-WBC semen groups. According to the assay results of normal males, Groups A and B were each subdivided into normal and decreased groups of sperm penetrating power, intact acrosome rate and terminal swelling rate.

RESULTSThe content of IL-1beta in the seminal plasma of the infertility group was obviously higher, but the content of IL-4, IL-10 significantly lower than that of the normal group (P < 0.01). In the infertility group, there existed significant differences in the contents of IL-1beta, IL-4, IL-10 in seminal plasma between the WBC and non-WBC semen groups, as well as between the AsAb positive and negative groups (P < 0.05 or P < 0.01); and the same was true for the content of IL-4 between the normal and decreased groups of sperm vitality, motility, penetrating power, intact acrosome rate, and terminal swelling rate (P < 0.05 or P < 0.01).

CONCLUSIONThe contents of IL-1beta, IL-4 and IL-10 in seminal plasma are closely related to male reproduction. The increase or decrease of the contents reflects the state of immunity and infection of the reproductive system, and influences sperm functions.

Adult ; Case-Control Studies ; Female ; Humans ; Infertility, Male ; immunology ; metabolism ; Interleukin-1 ; analysis ; Interleukin-10 ; analysis ; Interleukin-4 ; analysis ; Male ; Radioimmunoassay ; Semen ; chemistry ; Sperm Count ; Sperm Motility

Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of "biliary diseases with pancreatic counterparts." Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.
Adaptive Immunity ; Autoimmune Diseases/*immunology ; B-Cell Activating Factor/metabolism ; Cholangitis, Sclerosing/*immunology ; Cholecystitis/*immunology ; Humans ; Immunoglobulin G/*immunology ; Interleukin-10/metabolism ; Liver Diseases/*immunology ; Pancreatitis/*immunology ; T-Lymphocytes, Regulatory/immunology

OBJECTIVETo study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC).

METHODSSixteen patients with HCC associated with liver cirrhosis were divided into two groups: splenectomy combined with hepatectomy (n = 7) and hepatectomy (n = 9). T-lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th-lymphocyte cytokines such as IFN-gamma, IL2, IL10 in 7 ml peripheral venous blood before operation and two months after operation were examined and compared between the two groups.

RESULTSThere was no significant difference in pre-operative CD4, CD4/CD8, IL2, IFN-gamma, IL10 levels in the two group. Two months after operation, the levels of CD4 (38.2% +/- 3.7%), CD4/CD8 (1.7 +/- 0.3), IFN-gamma [(104.4 +/- 14.9) pg/ml], IL2 [(98.6 +/- 18.6) pg/ml] were increased and those of CD8 (23.7 +/- 13.7) pg/ml and IL10 [(55.5 +/- 11.2) pn/ml] were decreased in the two groups, but the changes in the group of splenectomy combined with hepatectomy were more obvious than those in the hepatectomy group. The levels of CD4 (32.5% +/- 4.0%), CD4/CD8 (1.1 +/- 0.1), IFN-gamma [(70.5 +/- 12.6) pg/ml], IL2 [(80.9 +/- 13.5) pg/ml] in the group of splenectomy combined with hepatectomy, were much higher than those in the hepatectomy group; those of CD8 (29.4% +/- 4.0%), IL10 [(89.4 +/- 10.0) pg/ml] level were significantly lower than those in the hepatectomy (P < 0.05).

CONCLUSIONSplenectomy combined with hepatectomy for HCC associated with liver cirrhosis donor decrease but promote the recover T-lymphocyte subsets and Th1/Th2 cytokines from imbalance and improve the patient's antitumor immune function.

CD4 Lymphocyte Count ; CD8-Positive T-Lymphocytes ; immunology ; Carcinoma, Hepatocellular ; immunology ; surgery ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Liver Cirrhosis ; immunology ; surgery ; Liver Neoplasms ; immunology ; surgery ; Splenectomy ; adverse effects

BACKGROUNDBoth ischemic preconditioning (IPC) and limb remote ischemic postconditioning (LRIPOC) have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury (IRI), but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.

METHODSEighty rats were randomly allocated into four equal groups: sham group, IRI group, IPC group and LRIPOC group. In 10 rats randomly selected from each group, serum levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 were assessed, and infarct size was determined. In another 10 rats of each group, myocardial levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 in both ischemic and non-ischemic regions were measured.

RESULTSThe infarct size was significantly lower in IPC and LRIPOC groups than in IRI group. The serum and myocardial levels of pro-inflammatory cytokines including TNF-α, HMGB1, ICAM1, IL-1 and IL-6 during reperfusion were significantly reduced in IPC and LRIPOC groups compared to IRI group. As compared to the IPC group, infarct size, serum level of TNF-α at 60 minutes of reperfusion, serum levels of HMGB1 and ICAM1 at 120 minutes of reperfusion, myocardial levels of TNF-α, ICAM1, IL-1 and IL-6 in the ischemic region, myocardial levels of ICAM1, IL-1 and IL-6 in the non-ischemic region were significantly increased in the LRIPOC group.

CONCLUSIONSIn the rats with myocardial IRI, IPC produces more powerful inhibitory effects on local myocardial and systemic inflammatory responses than LRIPOC. This may be partly attributed to more potent cardioprotection produced by IPC.

Animals ; HMGB1 Protein ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-1 ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Ischemic Postconditioning ; methods ; Ischemic Preconditioning ; methods ; Male ; Myocardial Reperfusion Injury ; immunology ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the influence of inhibition of stress on the survival rate, organ dysfunction and (Th)1/Th2 cytokine profiles of the rats with invasive infection in the wound at early postburn stage.

METHODSSprague-Dawley rats inflicted with 30% TBSA full thickness burn were randomly divided into A (n = 36, with immediate resuscitation), B (n = 36, with immediate resuscitation and lytic cocktail administration). After subeschar injection of 0.1 ml Pseudomonas aeruginosa (10(8) CFU/ml) on 3rd postburn day, the subeschar bacterial quantitative analysis, the survival rate at 96 hours after bacteria injection, the parameters of organ dysfunction and the mRNA expression of IL-2, IL-4, IL-10 and IFN-gamma were determined by corresponding methods.

RESULTSThe quantity of subeschar bacteria was larger than 1 x 10(5)/gram in both groups. The survival rate in B group (66.7 +/- 2.6)% was obviously higher than that in A group (33.3 +/- 1.7)%, (P < 0.01). Inflammatory infiltration and pathological changes in the internal organs in B group were alleviated obviously compared with A group. The expression of IL-2 mRNA in B group was significantly lower than that in A group before bacterial inoculation, but increased at 48 and 96 hours after bacterial inoculation, while it was lowered in A group at the same time points (P < 0.05). The expression of IFN-gamma mRNA in A group was significantly lower than that in B group (P < 0.01), while that of IL-4 and IL-10 mRNA in A group was evidently higher than that in B group (P < 0.05 approximately 0.01).

CONCLUSIONInhibition of the stress response during early postburn stage could be beneficial to the prevention of the bacterial invasion due to the changes in Th1/Th2 ratio.

Animals ; Burns ; metabolism ; microbiology ; Disease Models, Animal ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Pseudomonas Infections ; immunology ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Wound Infection ; therapy