Disease relevance of IL10

• The porcine IL-10 nucleotide sequence was found to be highly homologous to the rat, mouse, and human IL-10 counterparts and to one of the open reading frames from the Epstein-Barr virus [1].
• To evaluate variables influencing in vitro immune response induction, pig monocyte-derived DCs (moDCs) were treated with putative type-1 and type-2 antigens (Ags, killed Mycobacterium tuberculosis (Mtb) and hen egg white lysozyme (HEWL)) and recombinant porcine cytokines (IL-6, IL-10, IL-12, IFN-gamma and TNF-alpha) [2].
• This study implies that the induction of IL-10 production may be one of the strategies used by PRRSV to modulate host immune responses [3].
• These results indicated a strong involvement of IFN-gamma, and maybe IL-10, in the development of immunity against PRRS virus [4].
• In addition, when PBMCs from pigs immunized previously with classical swine fever virus (CSFV) vaccine were cultivated with the recall antigen, CSFV, in the presence of PRRSV, significant upregulation of IL-10 gene expression and reduction of IFN-gamma gene expression were observed [3].

High impact information on IL10

• To investigate the possible immunomodulatory role of IL-10, its expression during the induction of tolerance to kidney allografts by cyclosporin A in miniature swine was also investigated [1].
• Clones encoding porcine interleukin 10 (IL-10) were isolated from a cDNA library produced from phytohemagglutinin-activated pig peripheral blood mononuclear cells [1].
• Since tolerance is achieved by a short course of cyclosporin A, we have also studied the in vitro effect of this drug on IL-10 gene transcription in blood mononuclear cells and have found that cyclosporin A inhibits IL-10 gene activation in T cells but does not interfere with IL-10 transcription in lipopolysaccharide-activated cells [1].
• These results suggest that the overexpression of IL-10, observed in cell populations infiltrating grafts from tolerant animals, may be a function of monocytes and/or B cells [1].
• These data suggest that CTLA4Ig-induced inhibition of naive allogeneic T cell responses can be mediated through the generation of regulatory T cells via an IL-10-dependent mechanism [5].

Biological context of IL10

• Treatment of moDCs with HEWL increased IL-13 but not IL-12, IFN-gamma or IL-10 mRNA, suggesting a DC2 phenotype [2].
• A strong correlation between rejection and up-regulation of the IFN-gamma gene was observed, whereas animals with long-term tolerance showed low levels of IFN-gamma, but high levels of IL-10 gene transcription [6].
• Hemodynamic indices, oxygen transport variables, total and differential white cell counts, and serum concentrations of TNF and IL-10 were determined at frequent intervals before and after TNF-alpha administration and during the LPS infusion [7].
• The chemotaxis of granulocytes was measured in an assay chamber, and the cytokines IL-8 and IL-10 with an enzyme-linked immunosorbent assay [8].
• The lungs and broncho-alveolar lavage (BAL) cells were assessed both for virus replication and apoptosis; BAL fluids were examined for interleukin (IL)-1, tumour necrosis factor-alpha and IL-10 [9].

Anatomical context of IL10

• Virus-induced in vitro lymphocyte (cross-) proliferation and production of both a Th1-type (IFN-gamma) and a Th2-type (IL-10) cytokine response were demonstrated in cultures of peripheral blood mononuclear cells (PBMC) [10].
• Both IL-10 and IFN-gamma mRNA levels were increased in mucosa, whereas IL-6 and IL-12 mRNA were expressed in spleen [11].
• The expression levels of Type 1 (IFN-gamma, IL-12), Type 2 (IL-4, IL-6), pro-inflammatory (TNF-alpha) and regulatory (IL-10, TGF-beta) cytokines were assessed by RT-PCR in the intestinal mucosa and spleen [11].
• Our results show that the indirect presentation pathway of xenoantigens by huAPC to CD4+ lymphocytes is crucial in the response to porcine endothelial cells, and that IL-10 could be of therapeutic interest to prevent human lymphocyte activation by this pathway [12].
• In H pigs, infection increased the frequency of expression of mRNAs for interleukin-8 (IL-8), IL-10, and tumor necrosis factor alpha (TNF-alpha) in mononuclear cells from synovial membranes (SM) [13].

Associations of IL10 with chemical compounds

• In the present study, the effects of montelukast on the level of IL-10 and on the activation of NF-kappaB in the inflammatory airway of asthmatic guinea pigs were investigated [14].
• Both 150 and 300 nM CORT suppressed IL-10 at 24 h (P<0.05), but neither concentration affected IFNgamma at 24 h [15].
• In Experiment 1, DEX, at 150 and 300 nM, suppressed concanavalin (ConA)-stimulated IFNgamma at both 12 and 24 h in culture, and IL-10 at 24h (P<0.05) [15].
• Kinetics of the production of serum antibody levels and Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokines was studied in five pigs vaccinated with a synthetic tri-peptide vaccine (S3Pvac) against Taenia solium, a vaccine that has been shown protects pigs against naturally acquired infection [16].
• In vivo, dietary beta-glucan attenuated the increase of plasma IL-6 and TNF-alpha, and enhanced the increase of plasma IL-10 when pigs were challenged with LPS [17].

Regulatory relationships of IL10

• The role of TNF-alpha and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10 [18].
• In addition, peripheral blood IFN-gamma responses were diminished by either in vitro depletion of CD4 expressing cells or by in vitro treatment with porcine IL-10 [19].

Other interactions of IL10

• The present study shows that elevated levels of serum CRP and IL-10 were associated with PCV2-infected piglets that subsequently developed severe PMWS [20].
• The goal of this porcine study was to investigate the effect of V.A.C.((R)) Therapy on the systemic distribution of the inflammatory cytokines interleukin (IL)-6, IL-8, IL-10, and transforming growth factor-beta1 [21].
• Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age [20].
• WB cultures exhibited peak IL-2, IL-6, IL-8 and IL-10 mRNA levels at 24, 12, 6 and 24h, respectively [22].
• PBMC cultures demonstrated peak expression of IL-2, IL-6, IL-8 and IL-10 mRNA levels at 12, 24, 24 and 6h, respectively [22].

Analytical, diagnostic and therapeutic context of IL10

• Delayed expression and higher levels of IL-10 were observed in tolerant animals compared with animals rejecting their allografts [1].
• In addition, pig IL-10 caused inhibition of gamma-interferon gene transcription as determined by a bioassay [1].
• The level of IL-10 in broncho-alveolar lavage fluid was measured by enzyme-linked immunoadsorbent assay [14].
• CONCLUSIONS: Donor preconditioning with IL-10 may constitute an interesting pharmacologic approach to reduce IRI severity after liver transplantation [23].
• In conclusion, the cytokine mRNA imbalance, specially the increased mRNA levels of IL-10 in the thymus, jointly with the histopathological and haematological disorders, are highly indicative of a T-cell immunosuppression, enhancing the notion that the immune system of PMWS-affected pigs is severely impaired [24].

References