Reduced IL-12 Levels Research Articles

Effects of sweet potato vine silage supplementation on meat quality, antioxidant capacity and immune function in finishing pigs.

Sweet potato vine, the byproduct of sweet potato, has a highnutritional value. Silage is an effective solution for nutrientpreservation. This article explored the effects of sweet potato vine silage (SPVS) supplementation on meat quality, antioxidant capacity and immune function in finishing pigs. One hundred and eightyfinishing pigs (Berkshire × Licha Black) with a body weight of 74.54 ± 3.32 kg were randomly divided into three groups. The three groups were separately fed basal diet (Ctrl), Ctrl supplemented with 2.5% SPVS (LSPVS) or 5% SPVS (HSPVS) on a dry matter basis. Results showed that the eye muscle area in the LSPVS group was significantly increased. The carcass weight in the HSPVS was significantly reduced compared with Ctrl. For the meat quality, only cooking loss in both HSPVS and LSPVS was reduced while other indexes had no significant differences. For the antioxidant capacity, the hepatic level of glutathione (GSH) peroxidase (GSH-PX) was significantly upregulated in LSPVS but downregulated in HSPVS. In the serum, HSPVS decreased GSHlevel and increased GSH-PX level. HSPVS significantly reduced hepatic interleukin-1β (IL-1β) levels and LSPVS significantly reduced IL-12levels and increased IL-8and IL-6levels. Moreover, HSPVS and LSPVS promoted the secretion of immunoglobulin M (IgM) and IgGin the serum. Our data showed that low-dose SPVS supplementation improved carcass traits and high-dose SPVS supplementation increased immune function in finishing pigs, which provides a new alternative to improve animal health.

Effect of preeclampsia on human milk cytokine levels

Introduction: Preeclampsia (PE) is a systemic inflammatory disease, and its effect on human milk immune components is poorly understood.Objective: To investigate whether PE affects human milk cytokine levels.Methods: This was a prospective observational study involving mothers diagnosed with PE and with singleton pregnancy with no fetal malformation. The following cases were excluded: diabetes, chorioamnionitis, use of illicit drugs and alcohol, mastitis and congenital infection. In total, 228 mothers were studied and divided into two groups matched by gestational age: PE (n = 114) and normotensive (control, n = 114). Colostrum was collected from 24–72 hours postpartum, and mature milk was collected at the end of the first month. Cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α) were measured using flow cytometry. A generalized linear model with a gamma distribution was used to analyze the differences between groups versus time interaction.Results: The mean gestational age was 36 weeks. Increased IL-1 and IL-6 levels and reduced IL-12 levels in the colostrum were detected in PE, while in the mature milk, the IL-6 and IL-8 levels were lower than those of the control group.Conclusions: PE is associated with increased levels of inflammatory cytokines in colostrum and decreased levels in mature milk.

Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat

Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID), to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV) and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1β, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1β and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1β, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.

123. Corticosteroids, but not catecholamines, mediate stress- and surgery-induced suppression of plasma IL-12 levels in rats: A second-phase response of stress-induced immune perturbations

We recently reported that various stress paradigms suppress plasma IL-12 levels. The aim of this study was to elucidate potential neuroendocrine mediating mechanisms. Administration of prostaglandin-E2, epinephrine, and corticosterone, significantly reduced plasma IL-12 levels. However, when subjecting animals to stress or surgery, only the glucocorticoid-receptor blocker, mifepristone, and the COX-2 inhibitor, etodolac, but not α- or β-adrenergic blockers, attenuated the reduction of plasma IL-12 levels. As epinephrine administration did reduce IL-12 levels, we subjected adrenalectomized and sham-operated rats to epinephrine and/or corticosterone administration. While corticosterone reduced IL-12 levels in both conditions, epinephrine did so only in sham operated animals, indicating that its effects are mediated through elevated endogenous corticosterone levels, which we confirmed. In addition, blockade of prostaglandin production during surgery also reduced corticosterone levels, suggesting that at least some of the effects of prostaglandin are corticosterone-mediated. In accordance, but contrary to some reports, our in vitro studies indicated that corticosterone, but not prostaglandin-E2 or epinephrine, reduced spontaneous and induced IL-12 production levels. We thus hypothesize that stress-induced immune perturbations rely on two mechanisms: One mediated through activation of short-lasting processes by catecholamines and/or prostaglandins, and a second leading to long-lasting perturbations through glucocorticoids. IL-12 has a long half-life time and is prominent in inducing Th1 differentiation – a long lasting process that, as observed herein, is indeed suppressed through elevated corticosteroids, but not catecholamines.

IL-6 Mediates the Susceptibility of Glycoprotein 130 Hypermorphs to Toxoplasma gondii

IL-6 and IL-27 are closely related cytokines that play critical but distinct roles during infection with Toxoplasma gondii. Thus, IL-6 is required for the development of protective immunity to this pathogen, whereas IL-27 is required to limit infection-induced pathology. Paradoxically, these factors both signal through gp130, but little is known about how the signals downstream of gp130 are integrated to coordinate the immune response to infection. To better understand these events, gp130 Y757F mice that have a mutation in gp130 at the binding site for suppressor of cytokine signaling 3, a critical negative regulator of gp130 signaling, were infected with T. gondii. These mutant mice were acutely susceptible to this challenge, characterized by an early defect in the production of IL-12 and IFN-γ and increased parasite burdens. Consistent with the reduced IL-12 levels, IL-6, but not other gp130 cytokines, was a potent antagonist of IL-12 production by gp130 Y757F macrophages and dendritic cells in vitro. Moreover, in gp130 Y757F mice, blocking IL-6 in vivo, or administration of rIL-12, during infection restored IFN-γ production and protective immunity. Collectively, these studies highlight that a failure to abbreviate IL-6-mediated gp130 signaling results in a profound anti-inflammatory signal that blocks the generation of protective immunity to T. gondii.

IL-10 and IL-12 expression in breast cancer patients and effect of therapy

14016 Background: We investigated whether immune system impairment manifested by increased Interleukin-10 (IL-10) and reduced IL-12 levels occur in breast cancer patients and determined the effect ...

Indicators for early prediction of outcome in sepsis

Sepsis is still a major cause of postoperative morbidity and mortality. Numerous biochemical indicators have been evaluated regarding their potential in predicting prognosis in sepsis. Generally, one must differentiate between indicators: those for preoperative detection of patients at risk for lethal sepsis and those for early prediction of lethal outcome of septic complications. The first include the analysis of mononuclear phagocyte interleukin (IL)-12-synthesizing capability. Reduced IL-12 levels were associated with higher lethality. Cytokine-associated gene polymorphisms such as the loss of monocyte HLA-DR expression and homozygotism for the tumor necrosis factor B2 allele have a place in preoperative risk evaluation, as they were associated with worse prognosis in sepsis. Among the most important biochemical indicators for early prediction of lethal outcome in sepsis are decreased L-selectin and elevated IL-18, IL-6, and PCT plasma concentrations. Increased nuclear factor kappaB activity in mononuclear phagocytes and elevated calcitonin gene-related protein plasma concentrations were associated with unfavourable prognosis.

Vaccination of rhesus macaques with a recombinant measles virus expressing interleukin-12 alters humoral and cellular immune responses.

Lack of a vaccine for infants and immunosuppression after infection are problems associated with measles virus (MV). Because interleukin (IL)-12 has been used successfully as a vaccine adjuvant and because inhibition of IL-12 expression has been associated with immunosuppression during measles, the addition of IL-12 may enhance the immune response to MV. To determine the effect of IL-12 supplementation, rhesus macaques were vaccinated with a recombinant MV expressing IL-12; these macaques had increased interferon-gamma production by CD4(+) T cells, decreased production of IL-4, and lower levels of MV-specific immunoglobulin G4 and neutralizing antibody. Lymphoproliferative responses to mitogen were not improved. IL-12 supplementation altered the T helper type 2 bias of the immune response after MV vaccination, had a detrimental effect on the protective neutralizing antibody response, and did not improve other manifestations of immunosuppression. Reduced IL-12 levels are not the sole factor in MV-induced immunosuppression.

Reduced production of interleukin 12 by interferon γ primed alveolar macrophages from atopic asthmatic subjects

BACKGROUNDAsthma is characterised pathologically by an inflammatory pulmonary infiltrate rich in T helper (Th) 2 cells and eosinophils. Interleukin (IL)-12 is a heterodimeric cytokine critical for driving the development of...