Browsing by Subject "Interleukin-10"

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Open Access
Cytokine profiles of preterm neonates with fungal and bacterial sepsis.
(Pediatr Res, 2012-08) Sood, Beena G; Shankaran, Seetha; Schelonka, Robert L; Saha, Shampa; Benjamin, Danny K; Sánchez, Pablo J; Adams-Chapman, Ira; Stoll, Barbara J; Thorsen, Poul; Skogstrand, Kristin; Ehrenkranz, Richard A; Hougaard, David M; Goldberg, Ronald N; Tyson, Jon E; Das, Abhik; Higgins, Rosemary D; Carlo, Waldemar A; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
BACKGROUND: Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS). METHODS: In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined-FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3 and sepsis group was explored. RESULTS: Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-γ (IFN-γ), interleukin (IL)-10, IL-18, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) (P < 0.05). CONCLUSION: Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β, and TNF-α in FS, BS, or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.
Open Access
Opioid Self-Administration is Attenuated by Early-Life Experience and Gene Therapy for Anti-Inflammatory IL-10 in the Nucleus Accumbens of Male Rats.
(Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017-10) Lacagnina, Michael J; Kopec, Ashley M; Cox, Stewart S; Hanamsagar, Richa; Wells, Corinne; Slade, Susan; Grace, Peter M; Watkins, Linda R; Levin, Edward D; Bilbo, Staci D
Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, the long-lasting mechanisms that shape risk or resilience for drug addiction remain unclear. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation, and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10). We thus hypothesized that anti-inflammatory signaling may underlie the effects of early-life experience on later-life opioid drug-taking. Here we demonstrate that neonatal handling attenuates intravenous self-administration of the opioid remifentanil in a drug-concentration-dependent manner. Transcriptional profiling of the nucleus accumbens (NAc) from handled rats following repeated exposure to remifentanil reveals a suppression of pro-inflammatory cytokine and chemokine gene expression, consistent with an anti-inflammatory phenotype. To determine if anti-inflammatory signaling alters drug-taking behavior, we administered intracranial injections of plasmid DNA encoding IL-10 (pDNA-IL-10) into the NAc of non-handled rats. We discovered that pDNA-IL-10 treatment reduces remifentanil self-administration in a drug-concentration-dependent manner, similar to the effect of handling. In contrast, neither handling nor pDNA-IL-10 treatment alters self-administration of food or sucrose rewards. These collective observations suggest that neuroimmune signaling mechanisms in the NAc are shaped by early-life experience and may modify motivated behaviors for opioid drugs. Moreover, manipulation of the IL-10 signaling pathway represents a novel approach for influencing opioid reinforcement.
Open Access
Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.
(PLoS One, 2010-08-17) Chichlowski, Maciej; Westwood, Greg S; Abraham, Soman N; Hale, Laura P
BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10(-/-) mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. CONCLUSIONS/SIGNIFICANCE: Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.