| First Author | Islam Z | Year | 2003 |
| Journal | Toxicol Sci | Volume | 74 |
| Issue | 1 | Pages | 93-102 |
| PubMed ID | 12773775 | Mgi Jnum | J:126517 |
| Mgi Id | MGI:3761452 | Doi | 10.1093/toxsci/kfg119 |
| Citation | Islam Z, et al. (2003) Role of IL-1(beta) in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice. Toxicol Sci 74(1):93-102 |
| abstractText | Endotoxin (lipopolysaccharide, LPS) and the trichothecenes are microbial toxins that are frequently encountered in food and the environment. Coexposure to LPS and the trichothecene deoxynivalenol (DON, vomitoxin) induces corticosterone-dependent apoptosis in thymus, Peyer's patches, and bone marrow in mice. The purpose of this study was to test the hypothesis that interleukin-1beta (IL-1beta) plays a central role in corticosterone induction and subsequent leukocyte apoptosis in this model. Coexposure to LPS (0.1 mg/kg, ip) plus DON (12.5 mg/kg, po) was found to significantly upregulate splenic IL-1beta mRNA and IL-1beta protein expression in B6C3F1 mice, as compared to treatments with vehicle or either of the toxins alone. B6.129S7-IL1r1tm1Imx mice, which are functionally deficient for the IL-1 receptor 1, produced significantly less corticosterone upon coexposure to LPS plus DON than did corresponding wild-type (WT) C57BL/6J mice. Consistent with these findings, IL-1 receptor 1-deficient mice were recalcitrant to apoptosis induction in leukocytes as determined by assessment of DNA fragmentation assay and flow cytometry. Furthermore, intraperitoneal injection of IL-1 receptor antagonist (100 microgram/mouse, twice at 3 h intervals) in B6C3F1 mice significantly inhibited LPS plus DON-induced increases in plasma corticosterone, as well as apoptosis in thymus, Peyer's patches, and bone marrow. To confirm IL-1beta's capacity to induce apoptosis, B6C3F1 mice were injected with the cytokine (500 ng/mouse, ip) three times at 2 h intervals, and then corticosterone and apoptosis were monitored. Plasma corticosterone levels and thymus and Peyer's patch apoptosis in IL-1beta-injected mice were significantly higher at 12 h than in control mice. Plasma adrenocorticotropic hormone (ACTH) levels in LPS plus DON-treated B6C3F1 mice did not correlate with the induction of plasma corticosterone or leukocyte apoptosis. Taken together, the results indicate that IL-1beta is an important mediator of LPS plus DON-induced corticosterone and subsequent leukocyte apoptosis and, furthermore, this cytokine possibly acts through an ACTH-independent mechanism. |
