| Description |
Since the outbreak of the Spanish Toxic Oil Syndrome (TOS) in 1981, animal models have proven unsuccessful at reproducing the severity of this food-borne illness. The intoxication was attributed to the ingestion of aniline-denatured repressed oil illegally sole as pure olive oil. TOS was characterized by acute, subacute and chronic multi-system organ involvement including pulmonary dysfunction, server myalgias and intense peripheral eosinophilia. Weight loss was commonly experienced by TOS patients. In the experiments reported here, peripheral blood mononuclear cells (PBMC) from patients who suffered from TOS were injected intraperitoneally into immunodeficient mice. The gamma-c/Rag2 KO mice were utilized to test the hypothesis that after reconstitution with human PBMC from TOS patients, followed by feeding of implicated oil, the TOS manifestations were to reproduced. Four sets of negative controls were used: untreated mice, mice fed canola oil, mice reconstituted with PBMC from normal subjects and mice reconstituted with (normal or TOS) PBMC and fed canola oil Following the immune reconstitution, mice were fed implicated or non-implicated oil for a period of 8 weeks. At baseline, 4 and 8 week time points, peripheral blood counts were performed as well as measurement of plasma lactate dehydrogenase (LDH) and aspartate aminotranserase (AST) levels to assess organ damage. All animals were screened for human IgG on week 4 to confirm PBMC engraftment. Finally, on week 8, the major organs from each animal were harvested and examined for eosinophil infiltration and de-granulation by immunohistochemical staining to detect major protein (MBP) deposition. The immune reconstitution of mice with human PBMC occurred 99% of the time (n=122). Mice in the control groups failed to loose weight. Generally, there was a steady increase of hematological markers from baseline to 8 weeks. After the autopsy as week 8, 50% of the mice were screened for eosinophils and MBP deposition. Only a rare number of eosinophils were found in the tissues, in the differential counts and in the peritoneal lavages, Overall, these results do not support the hypothesis that feeding toxic oil to mice reconstituted with TOS PBMC can reproduce the Spanish Toxic Oil Syndrome. |
