Effect of systemic cytokines in the intestinal homeostasis: development of an experimental model. *ciety of Immunology Congress

PEDROTTI, LP, RODRÍGUEZ-GALÁN MC, CORREA SG.

Viña del Mar, Chile

Congreso; 9th Latin American Congress of Immunology (ALAI)-XII Chilean Society of Immunology Congress; 2009

Sociedad Latinoamericana y Sociedad Chilena de Inmunología

Cytokine imbalance in intestinal mucosa affects epithelium permeability and activates leukocytes. Mice injected with IL-12 cDNA (hydrodynamic gene transfer) increase    IL-12 and IFNg, vary leukocyte subset counts and express activation markers on splenocytes.  In this model we evaluated the effect of systemically increased IL-12 in intestinal mucosa.  Mice were injected with 1 mg cDNA control or pscIL-12 cDNA. After 7 days we evaluated in MLNs percentage and phenotype of leukocytes and cytokine production in stimulated cultures. We detected increase in percentage of dendritic cells CD11+ MHC II high (p<0.05) without changes in CD80/CD86 markers. CD8+ lymphocyte percentage diminished and CD4/CD8 ratio increased with treatment (p<0.05).  IFNg production was higher after IL-12 treatment (p<0.05). Kinetic studies showed maximal levels of IL-12 after 24-48 h and induction of TNFá by day four of injection. Transgenic OTI mice with ovalbumin specific TCR also produced more IFNg in stimulated cultures after IL-12 cDNA administration. Systemic release of inflammatory cytokines modifies percentage of APC and lymphocyte subsets recruited in MLNs as well as function of these cells both in conventional or transgenic mice. Changes in percentages or function of subsets could affect the anti-inflammatory balance in mucosal inductive sites and therefore compromise the intestinal homeostasis. Cytokine imbalance in intestinal mucosa affects epithelium permeability and activates leukocytes. Mice injected with IL-12 cDNA (hydrodynamic gene transfer) increase    IL-12 and IFNg, vary leukocyte subset counts and express activation markers on splenocytes.  In this model we evaluated the effect of systemically increased IL-12 in intestinal mucosa.  Mice were injected with 1 mg cDNA control or pscIL-12 cDNA. After 7 days we evaluated in MLNs percentage and phenotype of leukocytes and cytokine production in stimulated cultures. We detected increase in percentage of dendritic cells CD11+ MHC II high (p<0.05) without changes in CD80/CD86 markers. CD8+ lymphocyte percentage diminished and CD4/CD8 ratio increased with treatment (p<0.05).  IFNg production was higher after IL-12 treatment (p<0.05). Kinetic studies showed maximal levels of IL-12 after 24-48 h and induction of TNFá by day four of injection. Transgenic OTI mice with ovalbumin specific TCR also produced more IFNg in stimulated cultures after IL-12 cDNA administration. Systemic release of inflammatory cytokines modifies percentage of APC and lymphocyte subsets recruited in MLNs as well as function of these cells both in conventional or transgenic mice. Changes in percentages or function of subsets could affect the anti-inflammatory balance in mucosal inductive sites and therefore compromise the intestinal homeostasis.