Higher whole-blood selenium is associated with improved immune responses in footrot-affected sheep.

We reported previously that sheep affected with footrot (FR) have lower whole-blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in conjunction with routine control practices accelerates recovery from FR. The purpose of this follow-up study was to investigate the mechanisms by which Se facilitates recovery from FR. Sheep affected with FR (n = 38) were injected monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19 healthy sheep received no treatment. Adaptive immune function was evaluated after 3 months of Se supplementation by immunizing all sheep with a novel protein, keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. Innate immunity was evaluated after 3 months of Se supplementation by measuring intradermal responses to histamine 30 min after injection compared to KLH and saline, and after 15 months of Se supplementation by isolating neutrophils and measuring their bacterial killing ability and relative abundance of mRNA for genes associated with neutrophil migration. Compared to healthy sheep, immune responses to a novel protein were suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune assays. Neutrophil function was suppressed in FR-affected sheep, but was not changed by Se supplementation or WB-Se status. Sheep FR is associated with depressed immune responses to a novel protein, which may be partly restored by improving WB-Se status (> 250 ng/mL).

The relationship between endogenous cortisol, blood micronutrients, and neutrophil function in postparturient Holstein cows.

Neutrophil function, blood micronutrients, and cortisol concentrations were measured in 43 clinically healthy postparturient Holstein cows. Estimated 305-day mature equivalent milk production and neutrophil function were related to results of the blood micronutrient concentrations and neutrophil function tests. Cattle had low to normal zinc concentrations; normal to high selenium, vitamin E, and cortisol concentrations; and normal copper concentrations. Blood selenium (P = .03) and zinc (P = .027) concentrations were both significant predictors of neutrophil adhesion, and selenium (P < .001) was a significant predictor of neutrophil cytochrome C reduction (superoxide production). Fourteen of 20 (70%) cattle with blood selenium concentrations > 300 ng/mL had neutrophil adhesion, and 15 of 20 (75%) had cytochrome C reduction above the mean value for this group. There was also a significant correlation (r = 0.331; P = .037) between cytochrome C reduction and estimated milk production. These findings suggest that neutrophils from postparturient dairy cows with higher blood concentrations of selenium have greater potential to kill microbes, and that cattle with greater superoxide production may have higher milk production.

Investigating the onset of autoimmunity in A.SW mice following treatment with 'toxic oils'.

In 1981, over 20,000 people were struck with toxic oil syndrome (TOS). H-2s strains of mice have been shown to develop symptoms of TOS after exposure to toxic oil. We examined the effects of toxic oil on A.SW mice, which are susceptible to chemically-induced autoimmunity, but do not spontaneously develop autoimmune disease. Mice were treated with three types of toxic oil: CO756 (case oil from Spain), RSD99 (rapeseed oil with no 3-(N-phenylamino)-1-2-propanediol (PAP) derivatives) and RSA99 (rapeseed oil supplemented with PAP derivatives). Mercuric chloride treated mice were used as a positive control. After toxic oil treatment, there were no consistent differences in body weight or organ weight (liver, kidney, thymus and spleen) as a percent of body weight at any of these timepoints: 2.5, 5 or 10 weeks. We also found that treatment with toxic oil did not induce autoantibody formation or lead to increased serum levels of IgG1, IgG2a or IgE at these timepoints. Conversely, at all timepoints, there were significant increases in organ weight as a percent of body weight in the mercury treated mice. Additionally, mercuric chloride treated mice had elevated serum levels of IgG1, IgG2a and IgE and developed anti-nuclear and anti-collagen antibodies.

Immunoglobulin and autoantibody responses in MRL/lpr mice treated with 'toxic oils'.

The toxic oil syndrome (TOS) occurred in Spain in 1981 as a result of ingestion of oil mixtures containing aniline-denatured rapeseed oil. The disease afflicted almost 20000 people, resulted in more than 400 deaths, and mimicked an autoimmune disease in all patients. Phenilamine-propanediol (PAP) has been implicated as a possible etiologic agent of TOS but absence of an acceptable animal model to evaluate the autoimmune potential of the 'case oil' has hindered identification of the actual etiologic agent(s). The purpose of this study was twofold; (1) to develop an animal model of human disease to investigate the immunological etiology and pathogenesis of TOS and (2) to determine if the 'case oil' responsible for TOS and/or two synthesized oils either induced or exacerbated the systemic autoimmune disease that occurs spontaneously in the MRL/lpr mouse. The oils tested were a denatured rapeseed oil collected from a family (case oil) who were affected by the TOS (CO756), a rapeseed oil denatured with 2% aniline and enriched with a mixture of diesters of PAP (RSD), and a rapeseed oil denatured with 2% aniline but contained no diesters of PAP (RSA). Female MRL/lpr mice, 7 weeks of age, received orally either an undiluted (neat) or a 1:10 diluted dose of each test oil, canola oil (oil control), water (nai;ve control), or 50-ppm mercury (positive control). Half of each group was sacrificed after 5 weeks of exposure and the remaining mice after 10 weeks of exposure. Serum IgG1, IgG2a, IgE isotypes and antinuclear (ANA), collagen type II, histone, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and Sm autoantibody concentrations were determined after 5 and 10 weeks of exposure. The oils did not significantly affect the concentrations of the serum immunoglobulins, although a shift in the IgG1:IgG2a ratio towards IgG1 was noted from 12 to 17 weeks of age (5-10 weeks of treatment). The oils did however stimulate the systemic autoimmune response. The RSD neat treatment resulted in a nonsignificant but noted increase in autoantibodies to collagen (10 weeks), histone (10 weeks) and dsDNA (5 and 10 weeks). CO756 neat increased the serum levels of ANA (5 weeks), collagen (5 weeks) and dsDNA (5 and 10 weeks). The RSA 1:10 dilution increased ssDNA and dsDNA autoantibodies at 5 weeks. The results suggest that PAP is an active principle of these noted responses. These data, coupled with the toxicology and pathology data from this study (Toxicol. Path. 29 (2001) 630), revealed that the three oils incited induction of the lymphoproliferative syndrome and that the two oils containing PAP induced and enhanced the systemic autoimmune response that develops spontaneously at an early age in the MRL/lpr mouse. There was also a positive correlation noted between serum autoantibody concentrations and progression of the idiopathic autoimmune syndrome in the MRL/lpr mouse.